cholecalciferol and Osteomalacia

Calcium and phosphorus represent building material for bones. The supplier of these bone minerals is the hormone calcitriol, which originates from vitamin D, itself made by sunshine in human skin. Requirement for bone minerals is highest during phases of rapid growth, and no one grows faster than the foetus and the infant, making them particularly vulnerable. Deprivation of calcium, whether through low calcium intake or low vitamin D, leads to serious health consequences throughout life, such as hypocalcaemic seizures, dilated cardiomyopathy, skeletal myopathy, congenital and infantile rickets, and osteomalacia. These 5 conditions are often summarised as 'symptomatic vitamin D deficiency', are fully reversible but also fully preventable. However, the increasing prevalence of rickets and osteomalacia, and the deaths from hypocalcaemic cardiomyopathy, demand action from global health care providers. Clarification of medical and parental responsibilities is a prerequisite to deliver successful prevention programmes. The foetus and infant have the human right to be protected against harm, and vitamin D supplementation has the same public health priority as vaccinations.

Topics: Calcitriol; Calcium; Calcium, Dietary; Cardiomyopathy, Dilated; Cholecalciferol; Ergocalciferols; Female; Fetal Diseases; Humans; Infant; Infant, Newborn; Osteomalacia; Pregnancy; Pregnancy Complications; Rickets; Seizures; Vitamin D Deficiency; Vitamins

Oncogenic osteomalacia (OOM) is a rare paraneoplastic syndrome induced by tumor produced phosphaturic factors, i.e. phosphatonins. The disorder is characterized by renal tubular phosphate loss, secondary to this process hypophosphatemia and defective production of active form of vitamin D. The clinical course of oncogenic osteomalacia is characterized by bone pain, pathological fractures, muscle weakness and general fatigue. Osteomalacia-associated tumors are usually located in the upper and lower limbs, with half of the lesions primarily situated in the bones. Most of them are small, slow-growing tumors. Their insignificant size and various location coupled with rare occurrence of the disease and non-specificity of clinical symptoms lead to difficulties in reaching a diagnosis, which is often time-consuming and requires a number of additional tests. The average time between the appearance of the first symptoms and the establishment of an accurate diagnosis and the beginning of treatment is over 2.5 years. The aim of this study is to discuss the pathophysiology of disease symptoms, pathomorphology of tumors, diagnostic methods and treatment of oncogenic osteomalacia.

Topics: Biopsy; Bone and Bones; Cholecalciferol; Diagnostic Imaging; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Fractures, Spontaneous; Humans; Hypophosphatemia; Neoplasms, Connective Tissue; Osteomalacia; Pain; Paraneoplastic Syndromes; Somatostatin

Topics: Cholecalciferol; Diagnosis, Differential; Humans; Hypophosphatemia; Orthopedic Procedures; Osteomalacia; Prognosis; Receptors, Calcitriol; Sunlight; Vitamin D Deficiency

Topics: Cholecalciferol; Diagnosis, Differential; Fractures, Spontaneous; Humans; Hypophosphatemia; Osteomalacia; Phosphates; Prognosis; Rickets; Syndrome; Vitamin D Deficiency

Topics: Animals; Cholecalciferol; Diagnosis, Differential; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Hypophosphatemia; Neoplasms; Osteomalacia; Paraneoplastic Syndromes; Prognosis; Rickets

Topics: Adult; Age Factors; Bone Density Conservation Agents; Calcium; Cholecalciferol; Diagnosis, Differential; Female; Humans; Osteomalacia; Radiography; Sunlight; Vitamin D Deficiency

Topics: Adolescent; Adult; Child, Preschool; Cholecalciferol; Fanconi Syndrome; Female; Humans; Hypophosphatemia, Familial; Male; Osteomalacia; Osteoporosis; Phosphates; Vitamin D

Topics: 25-Hydroxyvitamin D 2; Calcitriol; Calcium; Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Ergocalciferols; Humans; Intestinal Absorption; Osteomalacia; Parathyroid Hormone; Vitamin D

Topics: 24,25-Dihydroxyvitamin D 3; Animals; Birds; Bone and Bones; Calcitriol; Calcium; Chemical Phenomena; Chemistry; Cholecalciferol; Cytochrome P-450 Enzyme System; Dihydroxycholecalciferols; Fluorine; Intestinal Absorption; Kinetics; Minerals; Mixed Function Oxygenases; Osteoclasts; Osteomalacia; Parathyroid Hormone; Receptors, Calcitriol; Receptors, Steroid; Rickets; Stereoisomerism; Steroid Hydroxylases; Vitamin D3 24-Hydroxylase

Vitamin D deficiency is common in the elderly, especially in patients with hip fracture. Elderly people infrequently stay outside in the sunshine, and nutrition is deficient in vitamin D. In addition, the hydroxylation of vitamin D into active metabolites decreases with age. Vitamin D deficiency ultimately leads to osteomalacia, but in an earlier stage it causes secondary hyperparathyroidism, which is accompanied by increased bone turnover and cortical bone loss. Along these pathways vitamin D deficiency may contribute to the pathogenesis of hip fractures. In a survey in Amsterdam vitamin D deficiency was observed in more than 60% of the patients with hip fracture. Transilial bone biopsy showed signs of high turnover and cortical bone loss in more than 20% of patients. The elderly which are institutionalized carry an increased risk. Prevention or vitamin D deficiency is possible by adequate exposure to ultraviolet light. Primarily, the elderly should be encouraged to go out into the sunshine regularly. Advice on nutrition may be given additionally. When sunshine exposure is negligible, as in many disabled and institutionalized elderly, a daily supplement of vitamin D3 400 IU should be given. Preventive measures have to be evaluated prospectively. Vitamin D deficiency is not the most important risk factors for hip fractures, but the easiest to correct.

Topics: Adult; Aged; Aging; Cholecalciferol; Hip Fractures; Humans; Hydroxylation; Hyperparathyroidism; Middle Aged; Nutritional Requirements; Osteomalacia; Sunlight; Vitamin D; Vitamin D Deficiency

Topics: Acidosis, Renal Tubular; Calcium; Cholecalciferol; Citrates; Glomerular Filtration Rate; Humans; Kidney Glomerulus; Kidney Tubules; Osteomalacia; Phosphorus; Vitamin D

Our perception of vitamin D has evolved since the early part of this century. As an active, dihydroxylated metabolite vitamin D is acknowledged today not as an essential dietary factor but rather as a major calciotropic hormone. This paper summarizes current understanding of the formation and action of vitamin D in health and disease. The importance of laboratory assessment of serum vitamin D metabolites in the diagnosis and management of disorders of calcium and phosphorus metabolism is discussed.

Topics: Adult; Animals; Calcium; Chemical Phenomena; Chemistry; Child; Cholecalciferol; Dogs; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Osteomalacia; Parathyroid Glands; Pregnancy; Rats; Receptors, Cell Surface; Rickets; S100 Calcium Binding Protein G; Vitamin D; Vitamin D Deficiency

Topics: Aged; Antibodies; Antigen-Antibody Complex; Cholecalciferol; Copper; Humans; Immunoglobulin M; Liver Cirrhosis, Biliary; Liver Transplantation; Mitochondria, Liver; Osteomalacia; Penicillamine

Many advances have been made in the past several years in our understanding of the metabolism and mechanism of action of vitamin D. Recognition of the clinical implications of this knowledge continues to grow. Despite these gains, however, many questions remain unanswered. These include the role of 24,25(OH)2D3 in physiologic processes, the nature of the contribution of vitamin D metabolism to bone growth and development, the responses of other possible target tissues such as the pancreas and parathyroid gland, and the further elucidation of interactions between vitamin D metabolites and parathyroid hormone in the maintenance of calcium and phosphorus homeostasis. The next decade of research is bound to bring insight into these and other questions.

Topics: Bone and Bones; Calcium; Chemical Phenomena; Chemistry; Cholecalciferol; Humans; Hydroxycholecalciferols; Hyperparathyroidism; Intestinal Mucosa; Kidney; Mixed Function Oxygenases; Osteomalacia; Parathyroid Glands; Phosphates; Pseudohypoparathyroidism; Rickets; Vitamin D

A rapidly growing understanding of the biochemical and physiological processes that underlie the metabolism of vitamin D has provided new insights into the pathogenesis of oestomalacia. Many of the vitamin D--resistant osteomalacia syndromes can now be explained on the basis of defects in the metabolic conversion of vitamin D to the biologically active dihydroxylated metabolite 1,25(OH)2D and perhaps, in some instances, to impairement of the actions of 1,25(OH)2D on target tissues. The availability of this new information has made possible the synthesis of 1-hydroxylated forms of the vitamin for therapeutic use in states of vitamin D resistance. Although many questions regarding the pathogenesis and most effective approaches in the management of osteomalacia remain unanswered, considerable progress has been made in this direction as a result of continued research on the subject.

Topics: Bone Neoplasms; Chemical Phenomena; Chemistry; Cholecalciferol; Dihydroxycholecalciferols; Ergocalciferols; Giant Cell Tumors; Humans; Hydroxycholecalciferols; Hypoparathyroidism; Hypophosphatemia, Familial; Kidney Failure, Chronic; Metabolism, Inborn Errors; Nephrectomy; Osteomalacia; Phosphates; Pseudohypoparathyroidism; Vitamin D; Vitamin D Deficiency

Topics: Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Feedback; Humans; Hypocalcemia; Kidney Diseases; Liver; Osteomalacia; Parathyroid Hormone; Rickets; Seasons; Ultraviolet Rays; Vitamin D

Briefly reviewed herein are some of the contemporary findings on the metabolism of vitamin D, and the biochemical and physiological effects of this steroid in the animal. Certainly the most accepted major action of vitamin D is to enhance the intestinal absorption of calcium. Historically, there is also considerable evidence that the vitamin D is required for the resorption of calcium from bone, thereby aiding in maintaining normal serum calcium levels. Increasing evidence is becoming available that vitamin D does have a direct effect at the kidney level, and that the absorption and metabolism of the phosphate ion is also significantly affected by this steroid. As a consequence of vitamin D administration to the rachitic animal, some molecular changes in the intestine have been identified and these include the induction of the vitamin D dependent calcium binding protein, an increase in intestinal levels of alkaline phosphatase and calcium ATPase, and a stimulation of the adenylate cyclase system. A hallmark of recent efforts is a further understanding of the metabolism of vitamin D and the formation of its most active form, 1,25-dihydroxycholecalciferol. All of this knowledge will prove valuable in the rational treatment of certain abnormalities of calcium and bone metabolism for which examples are already available.

Topics: Animals; Bone and Bones; Brain; Calcitonin; Calcium; Cell Membrane Permeability; Chickens; Cholecalciferol; Cyclic AMP; Dihydroxycholecalciferols; Humans; Hydroxycholecalciferols; Ileum; Kidney; Muscles; Osteomalacia; Parathyroid Hormone; Phosphorus; Protein Biosynthesis; Rats; Rickets; Vitamin D

Topics: Adolescent; Adult; Aged; Alkaline Phosphatase; Anticonvulsants; Bone Diseases; Child; Child, Preschool; Cholecalciferol; Diagnosis, Differential; Epilepsy; Female; Humans; Hypocalcemia; Infant; Male; Middle Aged; Osteomalacia; Phosphates; Rickets; Time Factors; Vitamin D; Vitamin D Deficiency

Topics: Alpha-Globulins; Animals; Biological Assay; Chickens; Cholecalciferol; Humans; Hydroxycholecalciferols; In Vitro Techniques; Kidney; Kidney Failure, Chronic; Liver; Mucous Membrane; Osteomalacia; Osteopathic Medicine; Protein Binding; Rats; Tritium; Vitamin D Deficiency

Topics: Biological Assay; Bone and Bones; Bone Diseases; Chemical Phenomena; Chemistry; Chemistry, Physical; Cholecalciferol; Chronic Disease; Humans; Kidney Diseases; Osteomalacia; Protein Binding; Radioimmunoassay; Research; Rickets; Vitamin D; Vitamin D Deficiency

Topics: Adipose Tissue; Animals; Bone and Bones; Calcium, Dietary; Cholecalciferol; Dihydrotachysterol; Ergocalciferols; Ergosterol; Fishes; Hormones; Humans; Intestinal Absorption; Intestine, Small; Keratins; Kidney; Liver; Muscles; Osteomalacia; Rickets; Sebaceous Glands; Skin; Skin Absorption; Ultraviolet Rays; Vitamin D

Topics: Aluminum; Bone Regeneration; Calcium; Calcium Carbonate; Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Dihydroxycholecalciferols; Ergocalciferols; Humans; Hydroxycholecalciferols; Intestinal Absorption; Osteitis Fibrosa Cystica; Osteomalacia; Parathyroid Glands; Phosphorus; Secretory Rate; Vitamin D

Topics: Animals; Bone and Bones; Calcium; Cholecalciferol; Dactinomycin; Humans; Kidney; Liver; Nephrectomy; Osteomalacia; Rats; Rickets; Skin; Vitamin D; Vitamin D Deficiency

Topics: Calcitonin; Calcium; Cholecalciferol; Humans; Hyperparathyroidism; Hypocalcemia; Kidney Failure, Chronic; Osteitis Fibrosa Cystica; Osteomalacia; Parathyroid Glands; Phosphorus

Topics: Adenosine Triphosphate; Alkaline Phosphatase; Animals; Calcitonin; Calcium; Cholecalciferol; Citrates; Humans; Kidney; Osteomalacia; Parathyroid Hormone; Phosphates; Rats; Rickets; Vitamin D; Vitamin D Deficiency

Bone health is influenced by the intake of both calcium and vitamin D.. Our objective was to evaluate the influence of calcium and vitamin D supplementation on PTH and bone turnover. SETTING, PATIENTS, AND DESIGN: At an ambulatory research center, 159 postmenopausal healthy white women participated in this double-blind, placebo-controlled parallel, longitudinal factorial study that was 6 months in duration.. Subjects were randomly allocated to 4 groups: 1) double placebo, 2) calcium (1200 mg daily) plus placebo, 3) vitamin D3 (100 μg) plus placebo, and 4) vitamin D3 and calcium. Serum and urine were collected fasting and 2 hours after a calcium load at baseline and at 3 and 6 months.. Serum PTH, cross-linked C-telopeptide (CTX), and procollagen type I N-terminal propeptide (P1NP) were measured.. Before study medication, a calcium load resulted in a decline in PTH and CTX and an increase in urinary calcium excretion. Serum CTX and P1NP declined over time with calcium supplementation but did not change with increased vitamin D intake. There was a decline in PTH in the vitamin D groups in the fasting state compared with placebo. Suppression of PTH was greater after a calcium load in the vitamin D groups. A calcium load decreased PTH and CTX and raised urinary calcium.. Fasting PTH declines with vitamin D supplementation. PTH declines after calcium intake. Supplementation of the diet with 1200 mg calcium/d reduces bone turnover markers, whereas supplementation with up to100 μg vitamin D3/d does not.

Topics: Aged; Bone and Bones; Bone Remodeling; Calcium; Calcium, Dietary; Cholecalciferol; Collagen Type I; Dietary Supplements; Female; Fractures, Bone; Humans; Longitudinal Studies; Middle Aged; Osteomalacia; Osteoporosis; Parathyroid Hormone; Peptide Fragments; Peptides; Placebos; Postmenopause; Procollagen; Vitamins

To determine whether long-term dietary supplementation with low doses of vitamin D helps to prevent bone loss and the development of osteoporosis or osteomalacia in out-patients with Crohn's disease.. A randomized controlled study.. The out-patient clinic of a tertiary centre (university hospital).. Seventy-five out-patients (31 men and 44 women, aged 16-77 years) with Crohn's disease.. All patients were randomly assigned to receive either an oral supplement of 1000 IU/day vitamin D for 1 year or no supplement. Bone mineral density, assessed in the distal part of the nondominant forearm using single photon absorptiometry, and serum levels of 25-hydroxyvitamin D, assessed using a competitive protein binding assay, were measured before and after the period of dietary supplementation.. Relative change of bone mineral density.. Serum levels of 25-hydroxyvitamin D increased in 57% of patients who received a supplement (compared with 37% of control patients). Bone mineral density decreased significantly in control patients [median -7%, interquartile range -12.6-(+0.4%)] but not in patients who received a supplement [median -0.2%, interquartile range -3.8-(+14%); P < 0.005]. Increases in bone mineral density were especially prevalent among patients who received the supplement and had normal serum levels of 25-hydroxyvitamin D (68%), whereas increases occurred in only 18% of patients with low serum levels of 25-hydroxyvitamin D (P = 0.008). Patients without an intestinal resection and receiving the vitamin D supplement had a marginally greater increase in bone mineral content than patients who had undergone a resection (P = 0.05).. Long-term oral vitamin D supplementation seems to be an efficient means of preventing bone loss in patients with Crohn's disease and could be recommended, especially for patients at high risk of osteoporosis.

Topics: Absorptiometry, Photon; Adult; Bone Density; Calcifediol; Cholecalciferol; Crohn Disease; Female; Humans; Male; Osteomalacia; Osteoporosis; Time Factors

The dose of vitamin D3 required to maintain normal serum 25-hydroxyvitamin D levels in epileptic patients was evaluated in a prospective study. Patients were divided into two groups, comprising 14 institutionalized and 18 non-institutionalized subjects; they were taking carbamazepine, phenytoin and phenobarbitone, alone or in combination. The study was divided into a dose titration stage and a further period of assessment on a fixed dose after attainment of normal serum 25-hydroxyvitamin D levels. Seventeen of the 18 non-institutionalized patients achieved normal levels over a period of 12 months; the remaining patient became normal after 15 months. The dose required to achieve normal levels ranged from 400 to 4000 IU/day; three patients required less than 2400 IU vitamin D3, 12 required 2400 IU and three required greater than 2400 IU. All institutionalized patients achieved normal levels over a period of 12 months; six patients required less than 2400 IU, six required 2400 IU and two required greater than 2400 IU vitamin D3. Raised alkaline phosphatase levels occurred in 11 patients, and reverted to normal in six patients during the initial return of 25-hydroxyvitamin D levels to normal. During the second 12 months, when patients were taking a fixed dose of vitamin D3, alkaline phosphatase increased in five patients who had achieved normal levels. During this phase normal 25-hydroxyvitamin D levels were not maintained in five patients. There was a significant seasonal variation of 25-hydroxyvitamin D levels institutionalized patients, being highest in June and lowest in December. Our findings show that while there was a wide range in the dose required to achieve normal serum 25-hydroxyvitamin D levels--between 400 and 4000 IU/day--78 per cent of patients responded to a dose of 2400 IU/day.

Topics: Adolescent; Adult; Alkaline Phosphatase; Anticonvulsants; Calcifediol; Calcium; Child; Cholecalciferol; Drug Administration Schedule; Epilepsy; Female; Humans; Male; Middle Aged; Osteomalacia; Prospective Studies; Risk Factors

A clinical trial carried out during the autumn/winter season in 46 institutionalized elderly subjects (35 women, 11 men) (group mean age = 83 +/- 2 years) revealed a severe deficiency in vitamin D in these subjects (25-hydroxyvitamin D level less than or equal to 3 ng/ml). After oral administration of 100,000 IU of vitamin D3, an increase in 25-hydroxyvitamin D levels above the 10 ng/ml threshold was observed and maintained for three months. A second dose, administered after 3 months, made it possible to sustain this level. No sign of toxicity was detected, notably no trace of hypercalcemia. In contrast, no change in the deficit (25-hydroxyvitamin D level less than or equal to 3 ng/ml) was seen in the placebo population. Three-monthly administration of the moderate dosage of 100,000 IU of vitamin D3 all year round would offer a simple, effective and risk-free system to counteract vitamin D deficiency in the elderly and of preventing the risk of osteomalacia, thus reducing the incidence of fractures.

Topics: Administration, Oral; Aged; Aged, 80 and over; Cholecalciferol; Drug Evaluation; Female; Fractures, Spontaneous; Humans; Hydroxycholecalciferols; Male; Osteomalacia; Vitamin D Deficiency

Circulating concentrations of hydroxylated metabolites of vitamin D were measured in seven Asian patients with histologically proven osteomalacia before and during treatment with either cholecalciferol (vitamin D3) or 1,25-dihydroxycholecalciferol. All patients showed an excellent clinical and biochemical response to treatment irrespective of type of vitamin D administered. Circulating concentrations of 25-hydroxycholecalciferol and 24,25, 25,26, and 1,25 dihydroxycholecalciferols were abnormally low in the untreated patients. In five patients treated with small doses of cholecalciferol (3000 units, 75 micrograms daily) the concentration of 1,25-dihydroxycholecalciferol rose rapidly to normal and reached supra-normal levels within 72 h. Raised concentrations (up to 200 pg/ml) were sustained for several months and then started falling to normal. Serum 24,25 and 25,26 dihydroxycholecalciferols rose only gradually, after circulating 25-hydroxycholecalciferol concentration had increased to normal. In contrast, in the two patients who received 1,25-dihydroxycholecalciferol (1 microgram daily) serum concentrations of this metabolite rose to normal and only occasionally exceeded the upper limit of normal. The highest concentration observed was 80 pg/ml. Healing of osteomalacia occurred, however, in these two patients in the absence of any measurable increases in 25-hydroxycholecalciferol and 24,25 or 25,26 dihydroxycholecalciferols which all remained abnormally low. Thus, it seems that 1,25-dihydroxycholecalciferol is the most important factor for the healing of vitamin D-deficient osteomalacia and that other hydroxy metabolites are unimportant.

Topics: Adolescent; Adult; Asia; Calcium; Cholecalciferol; Dihydroxycholecalciferols; Female; Humans; Hydroxycholecalciferols; Male; Middle Aged; Osteomalacia; Parathyroid Hormone; United Kingdom

No publications have reported on osteomalacia in patients receiving intermittent cyclical therapy with etidronate (a bisphosphonate) and undergoing long-term hemodialysis (HD).. We report on a 46-year-old Japanese man admitted to our hospital for further examination of left forearm pain. Maintenance HD was started at age 24 years, and the man had been on HD since then. At age 38 years, surgical parathyroidectomy was performed for secondary hyperparathyroidism; iliac crest bone biopsy performed at the same time showed osteitis fibrosa. The active vitamin D. We believe that intermittent cyclical etidronate therapy without administration of active vitamin D

Topics: Bone and Bones; Bone Density Conservation Agents; Calcitriol; Cholecalciferol; Etidronic Acid; Humans; Ilium; Male; Middle Aged; Osteitis Fibrosa Cystica; Osteomalacia; Renal Dialysis; Vitamin D Deficiency

Severe prolonged vitamin D deficiency can cause rickets or osteomalacia. Both can be prevented by sunshine exposure or vitamin D supplementation. Although New Zealand guidance does not recommend vitamin D supplementation for the general population, it can be considered for individuals at risk of vitamin D deficiency. Routine measurement of 25-hydroxyvitamin D (25OHD) is also considered unnecessary.. We investigated the rates of vitamin D supplementation, rickets and osteomalacia in New Zealand, and of 25OHD results in Auckland, over the last two decades.. Vitamin D prescriptions increased 14-fold, from 86,295/year to 1,215,507/year, between 2003 and 2019, with medication costs alone in 2019 being >$1 million. Despite these changes, the annual prevalence of hospital admissions for rickets, osteomalacia and unspecified vitamin D deficiency remained low and stable (10-20/year). 25OHD concentrations increased between 2002 and 2003 and between 2009 and 2019, and in the later time-period, 25OHD tests mainly identified individuals without vitamin D deficiency (40-50% >75nmol/L, 65-70% >50nmol/L and only 7-12.5% <25nmol/L).. Osteomalacia and rickets persist at low rates despite widespread, increasingly costly vitamin D supplementation and testing, which largely identifies individuals without vitamin D deficiency. These results suggest that vitamin D guidance and practice in New Zealand should change.

Topics: Blood Chemical Analysis; Cholecalciferol; Dietary Supplements; Humans; New Zealand; Osteomalacia; Practice Guidelines as Topic; Practice Patterns, Physicians'; Prevalence; Rickets; Risk Assessment; Vitamin D; Vitamin D Deficiency; Vitamins

Vitamin D and calcium deficiency has a higher incidence in the orthopedic-trauma surgery patient population than generally supposed. In the long term this can result in osteomalacia, a form of altered bone mineralization in adults, in which the cartilaginous, non-calcified osteoid does not mature to hard bone.. The current value of vitamin D and its importance for bones and other body cells are demonstrated.. The causes of vitamin D deficiency are insufficient sunlight exposure, a lack of vitamin D3 and calcium, malabsorption, and rare alterations of VDR signaling and phosphate metabolism. The main symptoms are bone pain, fatigue fractures, muscular cramps, muscle pain, and gait disorders, with an increased incidence of falls in the elderly. Osteopathies induced by pharmaceuticals, tumors, rheumatism or osteoporosis have to be considered as the main differential diagnoses.. In addition to the recording of symptoms and medical imaging, the diagnosis of osteomalacia should be ensured by laboratory parameters. Adequate treatment consists of the high-dose intake of vitamin D3 and the replacement of phosphate if deficient. Vitamin D is one of the important hormone-like vitamins and is required in all human cells. Deficiency of vitamin D has far-reaching consequences not only for bone, but also for other organ systems.

Topics: Bone Density Conservation Agents; Cholecalciferol; Diagnosis, Differential; Dietary Supplements; Evidence-Based Medicine; Humans; Osteomalacia; Treatment Outcome; Vitamin D Deficiency

Tumor-induced osteomalacia is a rare paraneoplastic syndrome characterized by hypophosphatemia and inappropriately normal or low 1,25-dihydroxyvitamin D.. Here, we report a 6-year postoperative follow-up of a patient with oncogenic osteomalacia with a distinctive skeletal manifestation. The latter was characterized by an almost linear lytic lesion of a few millimeters with irregular borders, mainly involving the trabecular compartment but extending into cortical shell, located in the middle third of the right fibula. Six years after tumor resection, a sclerotic repair with a complete recovery was observed. Furthermore, we monitored a striking increase in bone mineral density throughout the observation period, reaching a peak of 73% over basal values at lumbar spine after 2 years; at total femur and radius, the peak was 47.5 and 4.6% respectively, after 4 years from tumor resection.. We report for the first time that an osteolytic lesion may be part of the skeletal involvement in tumor-induced osteomalacia.

Topics: Bone Density; Bone Density Conservation Agents; Calcium, Dietary; Cholecalciferol; Combined Modality Therapy; Dietary Supplements; Female; Fibula; Fractures, Stress; Humans; Middle Aged; Nasopharyngeal Neoplasms; Neoplasms, Connective Tissue; Osteomalacia; Paraneoplastic Syndromes; Postoperative Complications; Radiography; Treatment Outcome; Up-Regulation

Bilateral femoral neck insufficiency fracture due to osteomalacia in pregnancy is an extremely rare condition. In this article, we report a 22-year-old female case with bilateral femoral neck fractures in whom the diagnosis was delayed due to the avoidance of ionising radiation and managing hip complaints by conservatively in pregnancy. She was treated surgically with internal fixation using cannulated screws and received medical treatment for vitamin D deficiency.

Topics: Adult; Bone Density Conservation Agents; Calcium Compounds; Cholecalciferol; Delayed Diagnosis; Female; Femoral Neck Fractures; Femur Neck; Fracture Fixation, Internal; Fractures, Stress; Humans; Magnetic Resonance Imaging; Osteomalacia; Pregnancy; Pregnancy Complications; Treatment Outcome; Vitamin D Deficiency

Topics: Anticonvulsants; Bone Density Conservation Agents; Carbamazepine; Cholecalciferol; Epilepsy; Humans; Male; Middle Aged; Muscular Diseases; Osteomalacia; Phenobarbital; Treatment Outcome

Treatment of vitamin D deficiency with vitamin D is a common procedure when taking care of elderly patients, calcium supplementation being added only when calcium dietary intake is insufficient. Here, we report the case of a 58-year-old female who was referred to our unit because of suspicion of Paget's disease of the skull, based on elevated serum alkaline phosphatase and high skull methylene diphosphonate-technetium uptake. She had been prescribed cholecalciferol (100,000 IU/month) and calcium salts for the past 7 months after discovery of severe vitamin D deficiency by her primary care physician. No specific skull bone lesions were observed on both X-ray and computerized tomography. Serum calcium, phosphate and 25(OH) vitamin D levels were normal, while serum C-terminal cross-linked telopeptide, bone alkaline phosphatase and calcitriol were high and daily urinary calcium excretion was low. We found that she had not been compliant with the calcium prescription while vitamin D had been thoroughly taken. We suspected osteomalacia due to calcium deficiency. Both skull uptake and biological abnormalities normalised in few months after adding calcium supplementation to the vitamin D treatment, and spine bone mineral density increased by 9.5 % after 14 months of full treatment. The present case illustrates the necessity for adequate calcium intake during vitamin D repletion to normalise bone mineralisation and turnover and maintain the skeletal integrity.

Topics: Alkaline Phosphatase; Bone Density; Bone Remodeling; Calcium; Cholecalciferol; Dietary Supplements; Female; Humans; Medication Adherence; Middle Aged; Osteomalacia; Vitamin D Deficiency

A 93 year-old woman with Paget's disease of bone had been treated with etidronate without interruption during 20 years. The daily dose was usual (5mg/kg/day) but this prescription had never been stopped by her physicians. Two fractures had already occurred in pagetic (right tibia) and non pagetic bones (right fibula) within the last 2 years, and she presented rib fractures, another right tibia fracture and right femur fracture during hospitalization time. X-rays films showed major osteolysis of left ulna and right tibia. Blood samples and technetium bone scan brought no evidence for sarcoma or lytic evolution of the disease. A transiliac bone biopsy on non pagetic bone site confirmed the diagnosis of osteomalacia (increased osteoid parameters), with secondary hyperparathyroidism (hook resorption). In Paget's disease of bone, continuous treatment by etidronate may induce generalized osteomalacia, and increase the risk of fracture in both pagetic and non-pagetic bones. Whereas physicians and pharmaceutical industry try to improve the observance of those drugs, this striking observation also points out that a prescription always needs to be updated.

Topics: Aged, 80 and over; Alkaline Phosphatase; Biopsy; Bone Density Conservation Agents; Calcification, Physiologic; Calcium Carbonate; Cholecalciferol; Etidronic Acid; Female; Femoral Fractures; Fibula; Fractures, Spontaneous; Humans; Hyperparathyroidism, Secondary; Iatrogenic Disease; Osteitis Deformans; Osteolysis; Osteomalacia; Parathyroid Hormone; Radionuclide Imaging; Rib Fractures; Tibial Fractures; Ulna; Vitamin D

Valproic acid (VPA) is a wide spread anticonvulsant and mood-stabilizing agent, the use of which is associated with hepatotoxicity, bone marrow suppression and osteomalacia. In the current paper we propose a possible mechanism of VPA-induced osteomalacia involving accelerated catabolism of 1α,25(OH)(2)-vitamin D3 (VD3) due to increased expression of CYP24. We demonstrate that VPA strongly potentiates CYP24 mRNA expression by VD3 in human hepatocytes (HH) and in human embryonic kidney cells (HEK293). By the method of gene reporter assay we found that VPA increases basal and VD3-inducible activity of CYP24 promoter (pCYP24-luc) in human liver adenocarcinoma (HepG2) and in HEK293 cells in dose-dependent manner. In order to delineate the role of inhibitory effects of VPA on histone deacetylase 1 (HDAC1), we compared the effects of VPA with trichostatin A (TSA) on basal and inducible levels of CYP24 mRNA and pCYP24-luc transactivation. Transactivation of CYP24 promoter by VD3 was enhanced in the presence of both TSA and VPA. In contrast, VD3-inducible expression of CYP24 mRNA was enhanced by VPA but not by TSA, implying that HDAC1 inhibition is not the major reason for VPA effects on CYP24. We examined the effects of VPA on mitogen-activated protein kinases as the important transcriptional regulators of VDR. VPA activated extracellular signal-regulated kinase (ERK) but not c-Jun-N-terminal kinase (JNK) and p38 MAPKs. In conclusion, VPA enhances transcriptional activity of VDR and increases expression of CYP24 mRNA in the presence of VD3 in physiological concentrations. The mechanism involves activation of ERK and partly the inhibition of HDAC1.

Topics: Anticonvulsants; Blotting, Western; Cholecalciferol; Dose-Response Relationship, Drug; Extracellular Signal-Regulated MAP Kinases; HEK293 Cells; Hepatocytes; Histone Deacetylase 1; Humans; Luciferases; Osteomalacia; Plasmids; Pregnane X Receptor; Receptors, Calcitriol; Receptors, Steroid; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Steroid Hydroxylases; Transfection; Valproic Acid; Vitamin D3 24-Hydroxylase

Paget's disease is a relatively rare disorder of the bone with only a few reports and case series observations from India. Hypocalcaemia is rare in Paget's disease, usually occurring as a consequence of therapy with bisphosphonates. We report a 65-year-old woman with Paget's disease who had hypocalcaemia secondary to vitamin D deficiency. On further evaluation, she also had severe osteoporosis. How vitamin D deficiency affects the diagnosis and monitoring of Paget's disease and the relationship between the three diseases are discussed. This case illustrates an interesting situation with abnormal bone turnover, remodelling and mineralisation in the form of Paget's disease with osteomalacia and osteoporosis.

Topics: Absorptiometry, Photon; Aged; Bone and Bones; Bone Density; Calcium Carbonate; Cholecalciferol; Diphosphonates; Female; Humans; Hypocalcemia; Imidazoles; Lumbar Vertebrae; Osteitis Deformans; Osteomalacia; Vitamin D Deficiency; Zoledronic Acid

Topics: Adult; Ascorbic Acid; Calcium; Cholecalciferol; Female; Fractures, Bone; Humans; Hypocalcemia; Osteomalacia; Pregnancy; Pregnancy Complications; Vitamin D Deficiency

Topics: Adult; Celiac Disease; Cholecalciferol; Female; Humans; Hyperparathyroidism, Secondary; Osteomalacia; Pregnancy; Pregnancy Complications

Osteomalacia is caused by impaired vitamin D receptor (VDR) signaling, calcium deficiency, and altered bone mineralization. This can be due to insufficient sunlight exposure, malabsorption, reduced D hormone activation in chronic kidney disease, and rare alterations of VDR signaling and phosphate metabolism. Leading symptoms are bone pain, muscular cramps, and increased incidence of falls in the elderly. The adequate respective countermeasures are to optimize the daily intake of calcium and vitamin D3 and to replace active D hormone and phosphate if deficient. Osteoporosis is characterized by bone fragility fractures upon minor physical impact. Indications for diagnosis and treatment can be established by estimating the absolute fracture risk, taking into account bone mineral density, age, gender, and individual risk factors. Exercise, intervention programs to avoid falls, and specific drugs are capable of substantially reducing fracture risk even in the elderly. Secondary osteoporosis primarily requires both bone-altering medications and effective treatment of underlying diseases.

Topics: Accidental Falls; Aged; Bone Density; Bone Density Conservation Agents; Calcium; Cholecalciferol; Combined Modality Therapy; Exercise; Fractures, Spontaneous; Hip Fractures; Humans; Middle Aged; Osteoblasts; Osteoclasts; Osteomalacia; Phosphates; Practice Guidelines as Topic; Receptors, Calcitriol; Risk Factors; Signal Transduction; Spinal Fractures; Vitamin D Deficiency

Topics: Aged; Aged, 80 and over; Back Pain; Calcium; Cholecalciferol; Diagnosis, Differential; Diphosphonates; Dose-Response Relationship, Drug; Female; Fractures, Compression; Fractures, Spontaneous; Humans; Lumbar Vertebrae; Osteomalacia; Osteoporosis, Postmenopausal; Radiography

Hypovitaminosis D is well known in different populations, but may be under diagnosed in certain populations. We aim to determine the first diagnosis considered, the duration and resolution of symptoms, and the predictors of response to treatment in female asylum seekers suffering from hypovitaminosis D.. A pre- and post-intervention observational study.. A network comprising an academic primary care centre and nurse practitioners.. Consecutive records of 33 female asylum seekers with complaints compatible with osteomalacia and with hypovitaminosis D (serum 25-(OH) vitamin D < 21 nmol/l). Treatment intervention: The patients received either two doses of 300,000 IU intramuscular cholecalciferol as well as 800 IU of cholecalciferol with 1000 mg of calcium orally, or the oral treatment only.. We recorded the first diagnosis made by the physicians before the correct diagnosis of hypovitaminosis D, the duration of symptoms before diagnosis, the responders and non-responders to treatment, the duration of symptoms after treatment, and the number of medical visits and analgesic drugs prescribed 6 months before and 6 months after diagnosis.. Two-sample t-tests, chi-squared tests, and logistic regression analyses were performed. Analyses were performed using SPSS 10.0.. Prior to the discovery of hypovitaminosis D, diagnoses related to somatisation were evoked in 30 patients (90.9%). The mean duration of symptoms before diagnosis was 2.53 years (SD 3.20). Twenty-two patients (66.7%) responded completely to treatment; the remaining patients were considered to be non-responders. After treatment was initiated, the responders' symptoms disappeared completely after 2.84 months. The mean number of emergency medical visits fell from 0.88 (SD 1.08) six months before diagnosis to 0.39 (SD 0.83) after (P = 0.027). The mean number of analgesic drugs that were prescribed also decreased from 1.67 (SD 1.5) to 0.85 (SD 1) (P = 0.001).. Hypovitaminosis D in female asylum seekers may remain undiagnosed, with a prolonged duration of chronic symptoms. The potential pitfall is a diagnosis of somatisation. Treatment leads to a rapid resolution of symptoms, a reduction in the use of medical services, and the prescription of analgesic drugs in this vulnerable population.

Topics: 25-Hydroxyvitamin D 2; Administration, Oral; Adult; Analgesics; Calcium; Chi-Square Distribution; Cholecalciferol; Drug Prescriptions; Emergencies; Female; Humans; Injections, Intramuscular; Logistic Models; Osteomalacia; Pain; Primary Health Care; Prospective Studies; Radioimmunoassay; Spectrophotometry; Time Factors; Vitamin D Deficiency

Hyperphosphatemia-hyperostosis syndrome (HHS) is a rare autosomal recessive metabolic disorder characterized by elevated serum phosphate levels and repeated attacks of acute, painful swellings of the long bones with radiological evidence of periosteal reaction and cortical hyperostosis. HHS shares several clinical and metabolic features with hyperphosphatemic familial tumoral calcinosis (HFTC), which is caused by mutations in GALNT3 encoding a glycosyltransferase responsible for initiating O-glycosylation. To determine whether GALNT3 is involved in the pathogenesis of HHS we screened two unrelated Arab-Israeli HHS families for pathogenic mutations in this gene. All affected individuals harbored a homozygous splice site mutation (1524+1G-->A) in GALNT3. This mutation was previously described in a large Druze HFTC kindred and has been shown to alter GALNT3 expression and result in ppGalNAc-T3 deficiency. Genotype analysis of six microsatellite markers across the GALNT3 region on 2q24-q31 revealed that the HHS and HFTC families share a common haplotype spanning approximately 0.14 Mb. Our results demonstrate that HHS and HFTC are allelic disorders despite their phenotypic differences and suggest a common origin of the 1524+1G-->A mutation in the Middle East (founder effect). The heterogeneous phenotypic expression of the identified splice site mutation implies the existence of inherited or epigenetic modifying factors of importance in the regulation of ppGalNAc-T3 activity.

Topics: Calcinosis; Calcium; Child; Cholecalciferol; Female; Haplotypes; Humans; Hyperostosis; Male; N-Acetylgalactosaminyltransferases; Neoplasm Proteins; Neoplasms; Osteomalacia; Parathyroid Hormone; Pedigree; Phosphates; Polypeptide N-acetylgalactosaminyltransferase; Sequence Analysis, DNA

Topics: Calcinosis; Calcium; Cholecalciferol; Humans; Hyperostosis; N-Acetylgalactosaminyltransferases; Neoplasm Proteins; Neoplasms; Osteomalacia; Parathyroid Hormone; Phosphates; Polypeptide N-acetylgalactosaminyltransferase

Topics: Adult; Afghanistan; Bosnia and Herzegovina; Cholecalciferol; Ethiopia; Female; Humans; Middle Aged; Osteomalacia; Pain; Refugees; Somalia; Vitamin D Deficiency

A 60-year-old Caucasian woman with a 1-year history of pain at the ribs, spine, and pelvis consulted at our Institute in March 1999. She brought a bone densitometry performed using a Lunar DPX densitometer that showed bone mineral density (BMD) measurements in the osteoporotic range at both the lumbar spine and the femoral neck. As a child she had had bowed legs and had been treated with ultraviolet radiation. Results of the laboratory test performed at our institute showed normal total serum calcium, repeated low serum P levels, and a low renal phosphate threshold with elevated total and bone fraction of alkaline phosphatase with normal intact parathyroid hormone (PTH). A diagnosis of hypophosphatemic osteomalacia due to renal phosphate leak was made. She began treatment with neutral sodium phosphate at 1.5 g/day and calcitriol 0.5 microg/day. Her serum P levels normalized, and there was a progressive decrease in alkaline phosphatase levels. The densitometry showed a very rapid increase in BMD values with normalization at the lumbar spine after 10 months of treatment. This case shows the importance of bone densitometry in the follow-up of patients with suspected osteomalacia.

Topics: Alkaline Phosphatase; Bone Density; Calcium; Cholecalciferol; Female; Humans; Hypophosphatemia; Middle Aged; Osteomalacia; PHEX Phosphate Regulating Neutral Endopeptidase; Phosphates; Phosphorus; Proteins

Topics: Adult; Calcium Citrate; Cholecalciferol; Emigration and Immigration; Female; Germany; Humans; Osteomalacia; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Medronate; Vitamin D; Vitamin D Deficiency

Topics: Adenocarcinoma; Aged; Bone Neoplasms; Cholecalciferol; Disease Progression; Fatal Outcome; Flutamide; Humans; Male; Osteomalacia; Phosphates; Potassium Compounds; Prostate-Specific Antigen; Prostatic Neoplasms; Tomography, X-Ray Computed

Chronic pancreatitis is a longlasting inflammatory disease manifested clinically in the advanced stage by malabsorption syndrome. Its manifestations include also changes in the calcium metabolism and the occurrence of osteoporosis and osteomalacia or their combination. The objective of the study was to assess the vitamin D3 blood concentration in patients with chronic pancreatitis. The group comprised 15 patients (8 men and 7 women), median age 45.0 years. The authors found a significantly reduced serum concentration of vitamin D3 (p < 0.01) in patients with chronic pancreatitis. They assume that vitamin D deficiency is one of the decisive causes of bone complications in prolonged pancreatitis. Supplementation with vitamin D or its metabolites is then a necessary part of preventive and therapeutic provisions.

Topics: Adult; Aged; Cholecalciferol; Chronic Disease; Female; Humans; Male; Middle Aged; Osteomalacia; Osteoporosis; Pancreatitis; Vitamin D Deficiency

We analyzed transiliac bone biopsy specimens from 30 end-stage renal failure patients, taken at the time of admission for CAPD training. Results were compared with values of iPTH, bone alkaline phosphatase, 1,25-dihydroxyvitamin D3, skeletal survey, quantitative computed tomography (QCT) and single photon absorptiometry (SPA) bone density measurements. Osteitis fibrosa was the most common histological diagnosis, present in 15 of the 30 patients (50%), with eight classified as "severe" and seven as "mild." Eight patients (27%) had adynamic bone lesion, four mixed renal osteodystrophy (13%), and two (7%) osteomalacia. The mean age of the adynamic group was higher than the osteitis fibrosa group (41 +/- 12.1 vs. 56 +/- 10.2 years; P < 0.01), and than the mixed group (39 +/- 7.5 vs. 56 +/- 10.2 years; P < 0.02). Levels of iPTH enabled discrimination between groups, but not between individual patients, and values correlated with bone alkaline phosphatase (r = 0.62; P < 0.001). Erosion of the terminal phalanges was seen on the plain X-rays of 7 of 15 patients with mild or severe OF, and in three patients with another diagnosis. The majority of patients (> 90%) had bone density measurements within the normal range. No significant correlation existed between QCT or SPA scores and any of the histomorphometric parameters, or iPTH. We conclude that iPTH is the most helpful non-invasive investigation in this group of patients. Plain X-ray of the hands is the most useful radiological investigation, but single measurements of bone density are not diagnostic.

Topics: Adult; Aged; Biopsy; Bone and Bones; Bone Density; Cholecalciferol; Female; Fibrous Dysplasia of Bone; Humans; Kidney Failure, Chronic; Male; Middle Aged; Osteomalacia; Parathyroid Hormone; Radioimmunoassay; Tomography, X-Ray Computed

The so-called "waddling gait" caused by paresis or mechanical insufficiency of the hip muscles is an ambiguous clinical guiding symptom. This pelvifemorally accentuated muscular weakness coinciding with pain in the range of the locomotor system should make one consider the diagnosis of osteomalacia due to deficiency of vitamin D, especially in Asian patients. In the present case, the course of investigation is described in detail, as well as the effective therapy. The diagnosis of this clinical picture ought to be familiar to any neurologist, since its more frequent appearance must be expected as an increasing number of Asians seek asylum in the years ahead. Social integration of the affected persons may be made easier by treatment on the lines described here.

Topics: Adult; Cholecalciferol; Diagnosis, Differential; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Gait; Humans; Lordosis; Neurologic Examination; Osteomalacia; Vitamin D Deficiency

During the last 4 years we observed four cases of neonatal rickets. The mothers of the infants suffered from osteomalacia for 1-3 years prior to its diagnosis shortly after the birth of their children. All four infants were born with craniotabes, and one infant had, in addition, a radial fracture. The diagnoses were confirmed by radiological and laboratory tests which revealed a rarefied bone structure, decreased serum 25-hydroxy-vitamin D and increased alkaline phosphatase levels in all patients. The disorder regressed under low-dose vitamin D3 therapy. As osteomalacia seems to be predominant in oriental women living in Berlin, it is necessary to consider vitamin D deficiency when clinical symptoms of this disease arise and to treat these women at least during pregnancy.

Topics: Cholecalciferol; Female; Humans; Infant, Newborn; Osteomalacia; Pregnancy; Pregnancy Complications; Rickets

Topics: Biopsy; Cholecalciferol; Female; Gastrectomy; Humans; Ilium; Middle Aged; Osteomalacia; Radiography

Topics: Adolescent; Adult; Aged; Alkaline Phosphatase; Calcium; Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Female; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Long-Term Care; Male; Middle Aged; Osteomalacia; Parathyroid Glands; Parathyroid Hormone; Phosphorus; Radiography; Receptors, Calcitriol; Receptors, Steroid; Renal Dialysis

The biological activities of free (D3) and sulfoconjugated (SD3) vitamin D3 were compared after 6 weeks of oral administration to D-deficient (-D) female rats which were mated in the meantime. Mothers and pups were sacrificed 1-2 days following parturition and mineral and hormonal plasma status was determined in mothers and bone mineral determinations and bone histomorphometric studies performed. In newborns, plasma levels of Ca, P and 25-hydroxyvitamin D (25(OH)D) were measured. After parturition, -D mothers had decreased body weight (BW) as well as decreased plasma levels of Ca, P and 1,25-dihydroxyvitamin D (1,25(OH)2D) associated with undetectable levels of 25(OH)D. Plasma levels of immunoreactive calcitonin and parathormone, by contrast, were higher than in vitamin D-replete (+D) control mothers. Bone histomorphometric analysis showed osteomalacia and secondary hyperparathyroidism in -D mothers. After parturition, -D +SD mothers had reduced BW compared to D-treated mothers and the plasma parameters measured were abnormal. Almost all bone histomorphometric parameters were found to be intermediate between +D and -D groups without reaching values of +D mothers. By contrast, -D +D mothers had most of the bone formation parameters identical to those of +D mothers. However, bone resorption was still higher while plasma levels of P and 25(OH)D remained slightly, but significantly lower than in +D mothers. In pups, plasma Ca in both D3- and SD3-treated groups was similar to values in +D-treated rats. However, pups from SD3-treated mothers still showed plasma levels of P and 25(OH)D lower than in +D pups. In conclusion, treatment with SD3 in -D mother rats significantly improves the biochemical plasma parameters of pups, but complete normalization can be achieved only in the D3-treated group. Our results show that when administered at equal amounts, SD3 has a much lower biological activity than D3 in -D female rats and cannot therefore replace vitamin D3 particularly during pregnancy.

Topics: Animals; Animals, Newborn; Body Weight; Bone and Bones; Calcifediol; Calcitriol; Calcium; Cholecalciferol; Female; Hyperparathyroidism; Osteomalacia; Parathyroid Hormone; Phosphorus; Pregnancy; Pregnancy Complications; Rats; Vitamin D Deficiency

Rats were gastrectomized, and the intestinal absorption and fecal excretion of cholecalciferol were studied following the administration of radioactive cholecalciferol, either by subcutaneous injection or with the aid of a gastric tube. From measurements of radioactivity in feces and sera it has been possible to establish that gastrectomy in rats results in impaired intestinal absorption and increased fecal excretion of cholecalciferol. These findings indicate that gastrectomy alters the nutritional status of vitamin D, and may explain the high incidence of osteomalacia as a complication of gastrectomy.

Topics: Animals; Cholecalciferol; Feces; Gastrectomy; Intestinal Absorption; Intestinal Mucosa; Male; Osteomalacia; Rats; Rats, Inbred Strains

Topics: Adult; Calcifediol; Cholecalciferol; Chondrosarcoma; Drug Resistance; Fanconi Syndrome; Female; Follow-Up Studies; Humans; Meningeal Neoplasms; Osteomalacia; Phosphorus

Five patients with primary biliary cirrhosis and vitamin D deficiency (serum 25-hydroxyvitamin D less than 6 ng/ml) are presented. All patients had low serum 24,25-dihydroxyvitamin D3 concentrations. Three patients had histological osteomalacia, negative calcium balance, and subnormal serum 1,25-dihydroxyvitamin D3. Malabsorption of a standard dose of [3H]vitamin D3 was found in three of four patients with steatorrhea, enabling the effective dose of vitamin D3 given to be calculated. Oral vitamin D3 400-4000 IU/day (effectively 400-1860 IU/day) resulted in a return to normal of the serum vitamin D metabolites, correction of the impaired intestinal calcium absorption and healing of the osteomalacia. Increases in serum calcium, phosphate, and the renal tubular reabsorption of phosphate occurred with a concomitant decrease in serum parathyroid hormone. It is suggested that osteomalacia in primary biliary cirrhosis is the end result of vitamin D deficiency; the hepatic and renal hydroxylations of vitamin D are normal and target tissues are responsive to endogenously produced metabolites of vitamin D.

Topics: Administration, Oral; Adult; Aged; Biopsy; Cholecalciferol; Dihydroxycholecalciferols; Humans; Ilium; Liver Cirrhosis, Biliary; Middle Aged; Osteomalacia; Time Factors; Vitamin D Deficiency

Two patients with moderate renal failure sustained spontaneous bilateral hip fractures during treatment with fluoride, calcium, and vitamin D for osteoporosis. They had been taking sodium fluoride (40-60 mg/day) for 11 and 21 months, respectively. Histological examination of a specimen of the bone showed severe fluorosis in the first case, and quantitative analysis of bone showed osteomalacia and skeletal fluorosis in the other case. These abnormalities were considered to be the consequence of excessive retention of fluoride due to renal insufficiency. As bilateral femoral neck fractures are very rare these data suggest a causal link between fractures and fluoride in patients with renal failure. Thus fluoride should be given at a lower dosage, if at all, to patients with even mild renal failure.

Topics: Aged; Bone and Bones; Calcium; Cholecalciferol; Drug Therapy, Combination; Female; Femoral Neck Fractures; Fractures, Spontaneous; Humans; Kidney Failure, Chronic; Osteomalacia; Osteoporosis; Sodium Fluoride

We report a rare case of Albright's syndrome associated with both a soft-tissue myxoma and hypophosphataemic osteomalacia. Renal tubular function was preserved, except for glycosuria. Serum levels of 1,25(OH)2 vitamin D3 were normal. Excision of the myxoma did not influence the biochemical abnormalities, nor did standard doses of vitamin D3 or 1 alpha-OH vitamin D3. The previously reported cases of hypophosphataemic osteomalacia associated with fibrous dysplasia and mesenchymal tumours are reviewed and the underlying mechanism discussed.

Topics: Cholecalciferol; Female; Fibrous Dysplasia of Bone; Humans; Hydroxycholecalciferols; Hypophosphatemia, Familial; Middle Aged; Myxoma; Osteomalacia; Soft Tissue Neoplasms; Syndrome

In order to clarify whether carbamazepine causes disturbances in calcium and bone metabolism were examined the effect of vitamin D2 or D3 in 30 epileptic outpatients. They had been treated for at least 1 year with carbamazepine given as monotherapy. The local bone mineral in the forearms and the total bone mineral was measured before and during treatment with the vitamins (4000 IU/day) for 24 weeks. The bone mineral was not significantly different from controls before the study and it remained unchanged in both treatment groups during the study periods. Similarly, the biochemical indices of bone metabolism were virtually unchanged during the treatment period. We, thus, conclude that epileptic patients on carbamazepine monotherapy have normal bone metabolism.

Topics: Adult; Aged; Bone and Bones; Carbamazepine; Cholecalciferol; Epilepsy; Ergocalciferols; Female; Humans; Male; Middle Aged; Minerals; Osteomalacia; Vitamin D

Recognition over the last ten years of the fact that vitamin D does not act as such, but must be converted into a hormonal form, has filled in the picture physiological endocrine regulation of calcium and phosphate homeostasis. While vitamin D has thus lost the dietetic significance associated with it for over 50 years. Nevertheless, new interpretations of the aetiopathogenesis of many demineralizing bone diseases are of much greater utility. Nor is it futuristic to suppose that all the biochemical parameters establishing one of the metabolisms that are under strict homeostatic control in the body, such as that of calcium and that of phosphate, are understood.

Topics: Bone Diseases; Calcium; Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Glucocorticoids; Humans; Hypoparathyroidism; Iatrogenic Disease; Intestinal Absorption; Osteomalacia; Osteoporosis; Phosphates; Rickets; Vitamin D

Elucidation of the vitamin D endocrine system and the availability of potent metabolites have led to new approaches to vitamin D therapy. The traditional management of exogenous (sunlight) or endogenous (malabsorption) vitamin D deficiency without evidence of disordered vitamin D metabolism has not changed, since it consists of treatment with vitamin D itself--a therapy which preserves the normal intrinsic mechanisms for regulating the rate of production of 1,25-dihydroxycholecalciferol. 1,25-DHCC and the analogue compound 1 alpha-CC should be reserved for treatment of hypocalcemia consequent on chronic renal failure or hypoparathyroidism, where 1-hydroxylation is lacking or impaired. Hypophosphatemic rickets has been treated with 1-hydroxylated compounds, with promising results; this use of the latter metabolites warrants further investigation. The use of vitamin D metabolites and of pharmacological doses of vitamin D itself must be regarded as substitution of a hormone or hormone precursors. Therefore, careful monitoring of serum and urine calcium is required in every patient receiving these compounds, in order to avoid excessive dosage. Special attention must be paid to patients with sarcoidosis since they often develop hypercalcemia after vitamin D or UV-light exposure, as a result of an intrinsic regulation defect in 1,25-DHCC synthesis.

Topics: Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydroxycholecalciferols; Humans; Hydroxycholecalciferols; Hypoparathyroidism; Osteomalacia; Phosphates; Vitamin D; Vitamin D Deficiency

Topics: Calcium Metabolism Disorders; Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Humans; Hypoparathyroidism; Osteomalacia; Osteoporosis; Phosphorus Metabolism Disorders; Renal Dialysis; Vitamin D

The objectives of this study were to evaluate the effects of vitamin D(3) (D(3)) and 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) on uremic bone disease independent of their action on the intestine. The histomorphology of tibial metaphyses in uremic (5/6 nephrectomized [5/6 Nx]) rats fed a low-calcium-low-phosphorus (LCLP) diet was compared with sham-operated (SO) rats fed an LCLP diet and 5/6 Nx rats fed an LCLP diet and given 15,000 IU D(3) or 5 units (135 ng) 1,25-(OH)(2)D(3) daily for 7 days. A marked osteomalacia characterized by an increased percentage of active and inactive trabecular osteoid surface and thickened growth plates developed in proximal tibial metaphyses in 5/6 Nx rats given the placebo, compared with SO rats. These bone changes were associated with relative hypophosphatemia, hypophosphaturia, and hypercalciuria in 5/6 Nx rats. In 5/6 Nx rats treated with D(3) or 1,25-(OH)(2)D(3) the growth plates had undergone mineralization and vascular invasion and were markedly reduced in thickness. Other parameters of osteomalacia in trabecular bone were not different from 5/6 Nx rats given the placebo. There was a significant decrease in osteoclasts per millimeter of trabecular surface perimeter in D(3)- and 1,25-(OH)(2)D(3)-treated rats. These bone changes were associated with hypercalcemia, hyperphosphatemia, and hyperphosphaturia, compared with 5/6 Nx rats given the placebo. It was concluded that in uremic rats fed the LCLP diet, shortterm treatment with either pharmacologic levels of D(3) or 1,25-(OH)(2)D(3) corrected only lesions in the growth plate. Osteoid seams were not reduced in treated rats, although the serum calcium-phosphorus product was elevated. The 5/6 Nx rat fed the LCLP diet appears to be a useful model for the rapid induction of uremic osteomalacia in adult animals.

Topics: Animals; Blood Urea Nitrogen; Calcitriol; Calcium; Cholecalciferol; Dihydroxycholecalciferols; Hydroxycholecalciferols; Male; Osteomalacia; Phosphorus; Rats; Tibia; Time Factors; Uremia

Topics: Bone Diseases, Metabolic; Cholecalciferol; Chronic Disease; Humans; Hydroxycholecalciferols; Liver Diseases; Osteomalacia; Osteoporosis; Vitamin D

Vitamin D deficiency is in most cases subclinical and can only be detected by blood vitamin assays or biochemical changes in phosphorus and calcium metabolism. Clinical and radiological osteomalacia is much less common. It is due to prolonged and profound hypovitaminaemia, which in turn depends upon a variety of factors, the main one being defective photosynthesis. Low vitamin D dietary intake apparently does not result in osteomalacia unless it is accompanied by insufficient exposure to sun. Malabsorption of cholecalciferol results from steatorrhoea of various origina. Disorders in hepatic 25-hydroxylation are due to drug enzymatic induction and seem to be unrelated to the state of the renal function. Disorders in renal 1,25-hydroxylation may be consecutive to reduced renal tissue, impaired stimulation, or inhibiton or even congenital lack of 1-alpha hydroxylase.

Topics: Adult; Animals; Cholecalciferol; Diet; Humans; Hydroxylation; Intestinal Absorption; Osteomalacia; Rats; Ultraviolet Rays; Vitamin D; Vitamin D Deficiency

1. The metabolism of an intravenous pulse-dose of 65 nmol (25 microgram) of double-isotope-labelled cholecalciferol has been studied in 28 individuals. The subjects comprised 19 with serum concentrations of 25-hydroxycalciferol (25-(OH)D) less than or equal to 25 nmol/l, of whom 12 had clinical osteomalacia, and nine with serum 25-(OH)D > 25 nmol/l (30-125 nmol/l). 2. The concentrations in serum of radioactive cholecalciferol, 25-hydroxycholecalciferol (25-(OH)D3) and the three dihydroxylated metabolites: 1,25-, 24,25- and 25,26-dihydroxycholecalciferol (1,25-(OH)2D3, 24,25-(OH)2D3 and 25,26-(OH)2D3) were measured for up to 10 days after the injection. 3. The temporal relationships between the formation of individual radioactive metabolites and factors apparently influencing their production are described and their molar concentrations in serum calculated. 4. Formation of radioactive 1,25-(OH)2D3 was detectable only in vitamin D-deficient subjects. Between individuals, its maximum serum concentration was correlated significantly and inversely with serum calcium but with not other measured variable. In the individual, concentrations of radioactive serum 1,25-(OH)2D3 varied directly with radioactive serum 25-(OH)D3. 5. The failure to detect formation of radioactive 1,25-(OH)2D3 in vitamin D-replete subjects suggests that current estimates of the daily turnover of the hormone in the normal individual may be severalfold too high. 6. Radioactive 25,26-(OH)2D3 was produced rapidly by all subjects and in greater amounts by vitamin D-deficient individuals. Between subjects and in the individual its concentration in serum correlated only with the radioactive serum 25-(OH)D3. Production of this metabolite appeared to be unregulated and dependent solely on the concentration of its precursor. 7. In vitamin D-replete subjects, production of 24,25-(OH)2D3 was also apparently determined by precursor concentration. In vitamin D-depleted subjects, production of radioactive 24,25-(OH)2D3 was variably delayed for up to or more than 10 days. 8. There appeared to be a constraint on the quantitative hepatic production of 25-(OH)D which is not explained by simple feed-back inhibition. 9. If sterols other than 1,25-(OH)2D3 are required to initiate the mineralization of osteomalacic bone, after correction of vitamin D deficiency in man, 25-(OH)D3 and 25,26-(OH)2D3 are produced sufficiently rapidly to meet this hypothetical requirement, but not 24,25-(OH)2D3.

Topics: Cholecalciferol; Dihydroxycholecalciferols; Humans; Hydroxycholecalciferols; Hydroxylation; Osteomalacia

The absorption of simultaneously administered equimolar doses of 14C vitamin D3 and 3H 25 hydroxyvitamin D3 (25-OH-D3) has been studied in controls and patients with a variety of gastrointestinal disorders. As assessed from peak radioactivity in the serum and from faecal excretion of radioactivity, malabsorption of both vitamin D3 and 25-OH-D3 occurred in patients with steatorrhoea. Malabsorption of vitamin D3 was greater than 25-OH-D3. The magnitude of malabsorption of these compounds was related to the severity of the steatorrhoea but was moderate enough to suggest that replacement therapy in patients with intestinal malabsorption should be accomplished with relatively small doses of vitamin D. The more potent vitamin D metabolites are probably unnecessary in this situation.

Topics: Adult; Aged; Cholecalciferol; Feces; Female; Humans; Hydroxycholecalciferols; Intestinal Absorption; Intestinal Diseases; Male; Middle Aged; Osteomalacia

Topics: Anticonvulsants; Cholecalciferol; Humans; Intestinal Absorption; Osteomalacia; Phosphates; Vitamin D; Vitamin D Deficiency

The process of chronic hypophosphatemic vitamin D-resistant rickets--observation of two cases. With the male patient--our first case--the disease was sporadic and had not been recognized for a long time. In his early adulthood it manifested itself as Umbauzonen (pseudofractures) in the larger context of active osteomalacia. It was possible to observe the pseudofractures before and while the patient was treated with drugs. High doses of vitamin D 3 and dosage of phosphate mitigated the complains although with respect to the radiological, scintigraphic, humoral and histological findings there was only slow improvement or no improvement at all.--The patient's daughter is affected by the disease as well. In her case the pathological signs of her bones became better when treated with vitamin D 3.

Topics: Adult; Bone and Bones; Bone Diseases; Child, Preschool; Cholecalciferol; Chronic Disease; Extremities; Female; Humans; Male; Osteomalacia; Phosphates; Radiography; Thorax

It is evident that there has been enormous progress within the last decade in our understanding of vitamin D metabolism and its interaction with calcium, phosphate, parathyroid hormone, and a number of other factors. As a result largely of therapeutic trials with various metabolites of vitamin D, we now know something of their probable involvement in the development of rickets and osteomalacia. We do not yet have a clear comprehension of exactly how these metabolites influence bone mineralization other than through their indirect effect on serum calcium and phosphate. Nonetheless it seems likely that at least one, and perhaps more, of the metabolites do exert a more direct effect. One must conclude that a deficiency of the 1alpha-hydroxylase is probably not the only defect in renal insufficiency, although it currently that there must well known. It is premature to go so far as to suggest that there must be another metabolite not being synthesized in the diseased or absent kidney.

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Bone and Bones; Calcification, Physiologic; Calcium; Cholecalciferol; Humans; Hydroxylation; Hypophosphatemia, Familial; Kidney Diseases; Minerals; Osteomalacia; Phosphates; Vitamin D

Parameters of mineral metabolism were examined in 6 patients with moderately severe anticonvulsant drug-induced osteomalacia. Compared to 15 matched controls, the patients exhibited significantly reduced serum calcium, inorganic phosphate, and 25-hydroxyvitamin D concentration, elevated serum alkaline phosphatase and immunoreactive parathyroid hormone (iPTH) concentration, reduced intestinal 47Ca absorption, reduced urinary calcium and increased urinary hydroxyproline excretion, and reduced forearm bone mass. Intestinal absorption of vitamin D3 was normal. Following 4 months of treatment with vitamin D3 (4000 units/day), serum 25-OHD concentration was increased to 3 times mean normal values and all parameters except serum iPTH, urinary calcium excretion, and forearm bone mass were returned to levels not significantly different from normal. Serum iPTH concentration was reduced by 39% (P less than 0.05); 24-h urinary calcium excretion rose by 98% (P less than 0.001), and forearm bone mass increased by 5.6% (P less than 0.05). It is concluded that moderate-dose vitamin D3 supplementation is effective in normalizing parameters of mineral metabolism in this disorder, despite evidence of resistance to the biologic effects of vitamin D.

Topics: Adult; Alkaline Phosphatase; Anticonvulsants; Bone and Bones; Calcium; Cholecalciferol; Epilepsy; Female; Humans; Hydroxycholecalciferols; Male; Osteomalacia; Parathyroid Hormone; Phosphates

A competitive protein binding assay for 1,25-dihydroxycholecalciferol has been developed using the hormone's nuclear receptor protein from chick intestinal mucosa. This nuclear receptor protein can be stored at -70 degrees C for several months and bound and free hormone can be separated easily with dextran coated charcoal. Results obtained using this assay agree well with those reported by other groups of workers. Serum levels of other vitamin D-3 metabolites, namely 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol have also been measured and are shown in relation to 1,25-(OH)2D3 levels.

Topics: Animals; Cell Nucleus; Cholecalciferol; Dihydroxycholecalciferols; Humans; Hydroxycholecalciferols; Hyperparathyroidism; Intestinal Mucosa; Kidney Failure, Chronic; Kinetics; Microchemistry; Osteomalacia; Radioligand Assay; Receptors, Drug

Renal bone disease was assessed for an average of 5.5 years in 9 patients on maintenance haemodialysis. The investigative methods included serial biochemical estimations, radiographic skeletal surveys and quantitative bone histology. Repeated bone mineral analyses and neutron activation analyses of a hand were also performed in order to monitor changes in skeletal calcium content. Before treatment, progressive osteodystrophy was demonstrated by all techniques. Following therapy with the vitamin D analogues, all patients noted symptomatic improvement; serum alkaline phosphatase reverted to normal and serum parathyroid hormone concentrations decreased. Radiographically, subperiosteal erosions healed while the histological features of osteomalacia and osteitis fibrosa were abolished. Both bone mineral and neutron activation analyses indicated that progressive skeletal demineralisation had been halted. However, a sustained increase in the overall mineral content of bone was not demonstrated. Thus, vitamin D therapy although improving the biochemical, radiological, and histological features of renal osteodystrophy may not restore bone mass to osteopenic bone.

Topics: Adult; Alkaline Phosphatase; Bone and Bones; Bone Diseases; Cholecalciferol; Female; Humans; Long-Term Care; Male; Minerals; Osteomalacia; Parathyroid Hormone; Periosteum; Radiography; Vitamin D

Topics: Adolescent; Adult; Berlin; Child; Cholecalciferol; Female; Germany, West; Humans; Infant, Newborn; Osteomalacia; Pregnancy; Sunlight; Transients and Migrants; Ultraviolet Rays; Vitamin D Deficiency

Topics: Adolescent; Adult; Animals; Bone and Bones; Bone Resorption; Calcium; Child; Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Humans; Hypoparathyroidism; Intestinal Mucosa; Kidney; Liver Cirrhosis, Biliary; Malabsorption Syndromes; Osteomalacia; Parathyroid Glands; Phosphorus; Rats; Renal Tubular Transport, Inborn Errors; Vitamin D

Vitamin D-deficient osteomalacia with pronounced secondary hyperparathyroidism was observed in an acromegalic patient suffering from adult celiac disease. Two oral tests with tritiated vitamin D3 showed a nearly normal absorption coefficient, contrasting with a marked steatorrhea mainly due to functional and reversible pancreatic insufficiency. The urinary excretion of the radioactive label was strikingly increased and accounted for the completely flat curve of plasma radioactivity. This urinary loss of mainly water-soluble metabolite(s) of vitamin D3 represents a unique and presently unexplained feature.

Topics: Acromegaly; Celiac Disease; Cholecalciferol; Female; Humans; Hyperparathyroidism, Secondary; Middle Aged; Osteomalacia

The effect of oral vitamin D3 therapy on calcium balance was compared in 18 institutionalized subjects with drug-induced osteomalacia and in 18 similar subjects without osteomalacia. The subjects with osteomalacia were receiving standard doses of phenytoin and phenobarbital. Diagnosis of osteomalacia was based on low serum calcium and phosphorus, elevated alkaline phosphatase, and appropriate roentgenographic bone changes. The study group achieved positive calcium balance at approximately 975 IU of vitamin D3 per day, while the control group achieved positive calcium balance at approximately 380 IU of vitamin D3 per day. The difference is highly significant (p less than 0.001). These data support previous observations that the osteomalacia of patients receiving anticonvulsant drugs is related to the drugs and that these patients require supplemental doses of vitamin D.

Topics: Adolescent; Adult; Anticonvulsants; Calcium; Cholecalciferol; Diet; Feces; Female; Humans; Male; Osteomalacia; Phenobarbital; Phenytoin

Topics: Child; Cholecalciferol; Female; Humans; Hyperparathyroidism; Hypocalcemia; Osteomalacia; Phosphates

In an adult with sporadic idiopathic osteomalacia an increased phosphate clearance, hypophosphataemia, normocalcaemia, normal serum-25-hydroxycalciferol and an only slightly increased immunoreactive parathormone were found. Intestinal 47Ca absorption was clearly decreased. Radiologically and histologically there was a clear-cut defect of skeletal mineralisation. Under treatment with daily doses of 1-1.25 mg of vitamin D3 the 25-hydroxycalciferol level increased markedly, the immunoreactive parathormone decreased slightly. Serum calcium and hypophosphataemia remained unchanged and intestinal 47Ca absorption was improved. Already 4 weeks after commencing treatment pain and defective gait of the patient disappeared. Radiologically skeletal changes were improved after 7 months. However, histologically no significant bone healing had occurred. The biochemical findings of this disease correspond to those of familial hypophosphataemic (vitamin-D-resistant) rickets. The therapeutic effects of pharmacological doses of vitamin D resemble those in pseudo-vitamin-D-deficient rickets. The pathogenesis of idiopathic osteomalacia of the adult remains unclear. Vitamin D metabolism is unchanged as far as the stage of 25-hydroxycholecalciferol. It is unknown if a disorder of the renal synthesis of 1,25-dihydroxycholecalciferol or a peripheral resistance to the effects of this metabolite exists. In addition a defect of the tubular phosphate reabsorption independent of parathormone and vitamin D is assumed.

Topics: Adult; Calcium; Cholecalciferol; Humans; Hydroxycholecalciferols; Intestinal Absorption; Male; Osteomalacia; Parathyroid Hormone; Phosphates

Topics: Aged; Cholecalciferol; Femoral Neck Fractures; Humans; Osteomalacia; Ozone; Ultraviolet Rays; Vitamin D Deficiency

In 54 epileptic outpatients treated for at least one year with anticonvulsants the bone mineral content (B.M.C.), an estimate of total body calcium, and serum calcium were measured before and during treatment with three doses of cholecalciferol (vitamin D3; 200, 100, and 50 mu-g daily) and 25-hydroxycholecalciferol (25-OHD3; 40, 20, and 10 mu-g daily) for 12 weeks. The results, when compared with the effects of calciferol (vitamin D2; 200, 100, and 50 mu-g daily) in 40 epileptic outpatients, showed different actions in anticonvulsant osteomalacia of vitamin D2 on the one hand and vitamin D3 and 25-OHD3 on the other. In the patients who received vitamin D2 an increase in B.M.C. was found whereas serum calcium was unchanged. The patients who received vitamin D3 or 25-OHD3 showed an increase in serum calcium but unchanged values of B.M.C. The results suggest that liver enzyme induction cannot alone explain anticonvulsant osteomalacia.

Topics: Anticonvulsants; Bone and Bones; Calcium; Cholecalciferol; Enzyme Induction; Epilepsy; Ergocalciferols; Humans; Hydroxycholecalciferols; Liver; Minerals; Osteomalacia

Topics: Alkaline Phosphatase; Bone and Bones; Calcium; Cholecalciferol; Epilepsy; Humans; Hydantoins; Hydroxylation; Osteomalacia; Time Factors; Vitamin D

Topics: Biopsy; Bone Neoplasms; Calcitonin; Calcium; Cholecalciferol; Humans; Hypocalcemia; Intestinal Absorption; Male; Middle Aged; Neoplasm Metastasis; Osteomalacia; Phosphorus; Prostatic Neoplasms

Severe osteomalacia with secondary hyperparathyroidism was observed in a 19-year-old mentally retarded girl, who had been treated for several years with antiepileptic drugs. Vitamin D3 orally administered in low doses led to complete reversal of all symptoms and normalization of blood chemistry, X-ray pictures demonstrated healing of all lesions. It is suggested that the alterations of vitamin-D metabolism occuring during the administration of phenobarbital and hydantion are of importance only in patients with an already lowered intake of vitamin D3 or reduced exposure to ultraviolet rays.

Topics: Adult; Anticonvulsants; Bicarbonates; Blood Proteins; Calcium; Cholecalciferol; Cholesterol; Creatinine; Female; Fractures, Bone; Hematocrit; Hemoglobins; Humans; Hyperparathyroidism; Osteomalacia; Vitamin B 12

Highly sensitive assays have been developed that enable 25-hydroxycholecalciferol (25-hydroxyvitamin D3) and 25-hydroxyergocalciferol (25-hydroxyvitamin D2) to be measured in the same serum sample. With these assays it has been shown that endogenously produced cholecalciferol (vitamin D3) is important in man; the findings further emphasize the role of vitamin D metabolites as hormones rather than vitamins in the traditional sense. Dietary sources of vitamin D appear to be inadequate and vitamin D deficiency has been shown to the cause of rickets and osteomalacia in Asian immigrants to Britain. This condition may be readily treated with small doses of vitamin D. In addition, sub-clinical deficiency was found in the Asian community. In the elderly, also, vitamin D deficiency was established as an important cause of osteomalacia and again evidence for the existence of a sub-clinical deficiency state was found. It is therefore suggested that the present prophylactic practices should be reviewed. Secondary hyperparathyroidism (reflected by elevated concentrations of circulating immunoassayable parathyroid hormone) was shown to be the rule rather than the exception in vitamin D deficiency. Some patients, however, had failed to respond to a hypocalcaemic stimulus. In others, there were high concentrations of parathyroid hormone despite normal serum calcium concentrations. Thus the relationship between parathyroid hormone and metabolites of vitamin D may not be mediated through changes in serum calcium alone, and it is postulated that metabolites of vitamin D may directly affect the secretion of parathyroid hormone.

Topics: Adolescent; Adult; Aged; Alkaline Phosphatase; Animals; Asia; Asian People; Child; Cholecalciferol; Ergocalciferols; Ethnicity; Humans; Hydroxycholecalciferols; Hyperparathyroidism, Secondary; London; Middle Aged; Osteomalacia; Parathyroid Hormone; Radioimmunoassay; Rats; Rickets; Submarine Medicine; United Kingdom; Vitamin D; Vitamin D Deficiency

Calcium and folic acid absorption were studied in 28 adult male epileptics on chronic anticonvulsant therapy. In 16 patients on diphenylhydantoin alone, calcium absorption was abnormal in 9. In 12 patients on both diphenylhydantoin and phenobarbital, calcium absorption was abnormal in 3 patients. Folic acid (3H-PGA) absorption was normal in all but one patient, while serum folate (less than 6.4 ng/ml) was reduced in all patients. Hypocalcemia (less than 8.5 mg/100 ml) occurred in only 2 patients, while serum alkaline phosphatase was elevated in 7 patients. These findings support the proposal that rickets and osteomalacia reported in patients on chronic anticonvulsant therapy results from reduced calcium absorption. The effect of these drugs appears to be the acceleration of the metabolism of vitamin D and an increase in the excretion of polar metabolites. This may result in reduced levels of 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol which are necessary for normal absorption of calcium. Since calcium absorption may be impaired secondary to a relative vitamin D deficiency, a supplemental increase in vitamin D intake by patients on anticonvulsant drugs is recommended.

Topics: Adult; Aged; Calcium; Cholecalciferol; Epilepsy; Folic Acid; Humans; Male; Middle Aged; Osteomalacia; Phenobarbital; Phenytoin; Rickets; Time Factors

The authors report osteomalacia in 3 cases of epilepsy and one case of coronary heart disease treated with phenobarbitone, either alone or associated with other anticonvulsants. There were clinical signs in all cases and typical radiological signs in 3 cases, a characteristic laboratory syndrome in 4 cases. In the 3 cases where it was estimated, serum levels of parathormone were high. Finally, in 3 cases where it was measured, daily urinary excretion of glucaric D acid was increased. The bony histological signs studied in 3 cases, were similar to those in deficiency osteomalacia. A study of Ca45 metabolism in one case, showed the characteristic changes found in osteomalacia. Finally, a study of the metabolism of tritiated vitamin D, or tritiated 25 OH CC, carried out in 3 cases, gave 3 different patterns; only one of them was characteristic of enzyme induction under the dependency of anticonvulsant. Started in 2 cases, treatment with 125 OH2CC, brought about a rapid fall in blood PTH levels which then rose again before falling progressively in one case, under treatment with 25 OH CC. The bony histological signs of hyperparathyroidism then regressed whilst serum PTH levels remained high. Phosphorous and calcium balance improved in only one case. Treatment with 25 OH CC in high dosage brought about clinical, radiological and laboratory cure of osteomalacia in both cases, reducing the frequency of fits in the epileptic patient.

Topics: Adult; Aged; Anticonvulsants; Calcium; Cholecalciferol; Female; Humans; Hydroxycholecalciferols; Hyperparathyroidism, Secondary; Hypnotics and Sedatives; Male; Middle Aged; Osteomalacia; Parathyroid Hormone; Phenobarbital; Phenytoin

Topics: Adolescent; Adult; Alkaline Phosphatase; Calcium; Child; Cholecalciferol; Diet; Diet, Vegetarian; Ergocalciferols; Female; Humans; Hypocalcemia; Male; Middle Aged; Osteomalacia; Phosphorus; Rickets; Seasons; United Kingdom; Vitamin D Deficiency; White People

Topics: Animals; Bone and Bones; Calcium; Chickens; Cholecalciferol; Eggs; Female; Fertilization; Osteomalacia; Phosphorus; Poultry Diseases

Topics: Animals; Bone Diseases; Calcium; Chemical Phenomena; Chemistry; Cholecalciferol; Dihydrotachysterol; Dihydroxycholecalciferols; Disease Models, Animal; Humans; Hydroxycholecalciferols; Isomerism; Kidney Failure, Chronic; Microradiography; Osteitis Fibrosa Cystica; Osteomalacia; Phosphates; Rats; Renal Dialysis; Uremia; Vitamin D

Topics: Animals; Anticonvulsants; Avitaminosis; Body Weight; Calcium; Calcium Radioisotopes; Cholecalciferol; Enzyme Induction; Epilepsy; Humans; Hypocalcemia; Intestinal Absorption; Liver; Long-Term Care; Mice; Osteomalacia; Phenobarbital; Phenytoin; Rats; Vitamin D

Topics: Adult; Aged; Bone Diseases; Calcitonin; Child; Cholecalciferol; Ergocalciferols; Humans; Hypercalcemia; Metabolic Diseases; New Zealand; Organophosphonates; Osteitis Deformans; Osteomalacia; Osteoporosis; Parathyroid Hormone; Sarcoidosis; Vitamin D; Vitamin D Deficiency

Topics: Adult; Age Factors; Cholecalciferol; Humans; Osteomalacia

Topics: Calcium; Carbon Isotopes; Cholecalciferol; Chromatography; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydroxycholecalciferols; Humans; Hydroxycholecalciferols; Intestinal Absorption; Kidney; Kidney Failure, Chronic; Osteomalacia; Tritium; Vitamin D Deficiency

Topics: Adult; Age Factors; Aged; Child; Cholecalciferol; Humans; Osteomalacia; Osteoporosis; Rickets; Sex Factors; Ultraviolet Rays; United Kingdom; Vitamin D; Vitamin D Deficiency

Topics: Bone and Bones; Bone Diseases; Cholecalciferol; Humans; Osteomalacia; Rickets; Ultraviolet Rays; Ultraviolet Therapy; Vitamin D Deficiency

Vitamin D deficiency is a previously unreported complication of therapy with hypnotics, and we here report a case of osteomalacia associated with long-term glutethimide administration. There was evidence of pronounced hepatic enzyme induction, and the plasma half-time of (3)H vitamin D(3) was decreased by this drug. In addition, raised levels of serum gamma-glutamyl transpeptidase, 5-nucleotidase, and leucine aminopeptidase were observed and the patient excreted large amounts of xylulose. These changes were reversed by stopping the glutethimide.

Topics: Cholecalciferol; Enzyme Induction; Female; gamma-Glutamyltransferase; Glutethimide; Half-Life; Humans; Leucyl Aminopeptidase; Liver; Middle Aged; Nucleotidases; Osteomalacia; Pentoses; Tritium

Topics: Administration, Oral; Alkaline Phosphatase; Anticonvulsants; Biopsy; Calcium; Carbamazepine; Child; Cholecalciferol; Epilepsy, Tonic-Clonic; Humans; Ilium; Iron; Long-Term Care; Male; Osteomalacia; Phenobarbital; Phenytoin; Phosphorus; Primidone; Rickets

Topics: Anticonvulsants; Bone and Bones; Bone Resorption; Calcium; Cholecalciferol; Humans; Hydroxycholecalciferols; Hydroxylation; Intestinal Absorption; Intestinal Mucosa; Kidney Failure, Chronic; Liver; Osteomalacia; Vitamin D; Vitamin D Deficiency

Topics: Animals; Calcium; Cholecalciferol; Diet; Hypocalcemia; Hypophosphatemia, Familial; Inositol; Male; Nutritional Requirements; Osteomalacia; Rats; Spectrophotometry, Atomic

Topics: Age Factors; Alkaline Phosphatase; Animals; Anticonvulsants; Calcium; Cholecalciferol; Enzyme Induction; Epilepsy; Humans; Liver; Osteomalacia; Rats; Vitamin D

Topics: Animal Nutritional Physiological Phenomena; Animals; Body Weight; Bone and Bones; Calcium; Calcium Isotopes; Cholecalciferol; Deficiency Diseases; Hydroxycholecalciferols; Hypercalcemia; Intestinal Mucosa; Intestine, Small; Kidney; Lipid Metabolism; Liver; Male; Osteomalacia; Phosphorus; Rats; Rickets; Tritium; Urine

The metabolic fate of intravenously injected vitamin D(3)-1,2-(3)H (D(3)-(3)H) was studied in two normal individuals on chronic phenobarbital therapy. Silicic acid column chromatography of lipid-soluble plasma extracts obtained serially for 96 hr after D(3)-(3)H injection demonstrated a decreased plasma D(3)-(3)H half-life and increased conversion to more polar metabolites. The polar metabolites formed included several with chromatographic mobility similar to known biologically inactive vitamin D metabolites and one with chromatographic mobility identical to 25-hydroxycholecalciferol. Disappearance of this latter material was also accelerated. A child with rickets and a normal volunteer studied before and after a 2 wk course of phenobarbital therapy demonstrated similar alterations in D(3)-(3)H metabolism. When liver microsomes from 3-wk-old Sprague-Dawley rats treated with phenobarbital were incubated with D(3)-(3)H, polar metabolites were produced with chromatographic mobility similar to the plasma D(3)-(3)H metabolites from phenobarbital-treated humans. Similar incubations employing 25-hydroxy-cholecalciferol-26-27-(3)H as the substrate also demonstrated an increased conversion to polar metabolites. The data suggest that the reported increased incidence of osteomalacia observed in patients on chronic anticonvulsant therapy may be the result of an accelerated conversion of vitamin D and its active metabolite, 25-hydroxycholecalciferol, to polar metabolites by druginduced liver microsomal enzymes.

Topics: Adult; Animals; Anticonvulsants; Cholecalciferol; Chromatography, Thin Layer; Enzyme Induction; Female; Half-Life; Humans; Hydroxycholecalciferols; Metabolic Clearance Rate; Microsomes, Liver; Middle Aged; Mixed Function Oxygenases; Osteomalacia; Phenobarbital; Phenytoin; Rats; Tritium

Topics: Adult; Alkaline Phosphatase; Body Height; Body Weight; Calcium; Child, Preschool; Cholecalciferol; Ergocalciferols; Female; Humans; Hydroxyproline; Hypophosphatemia, Familial; Male; Osteomalacia; Phosphates; Phosphorus; Radiography; Wrist

Topics: Animals; Cholecalciferol; Chromatography, Thin Layer; Female; Humans; Hydroxycholecalciferols; Male; Methods; Osteomalacia; Protein Binding; Radiochemistry; Rats; Tritium; Vitamin D Deficiency

Topics: Adult; Aged; Animals; Anticonvulsants; Cholecalciferol; Epilepsy; Female; Humans; Hydroxylation; Intestinal Absorption; Liver; Male; Middle Aged; Osteomalacia; Phenobarbital; Rats; Spectrum Analysis; Tritium

Plasma levels of 25-hydroxycholecalciferol (25-HCC) were measured by a specific competitive protein-binding assay. Mean levels in both normal London adults and adolescent schoolchildren were 16 ng/ml and the mean level in a group of epileptic patients on high-dosage anticonvulsant therapy was 5 ng/ml, (difference from normals P < 0.001). Two further epileptic patients, with well-marked anticonvulsant osteomalacia, were treated with small doses of 25-HCC during full metabolic balance studies; rapid healing followed administration of 25-HCC by mouth in doses of 10-45 mug daily, which is well below the effective dose range of calciferol in this condition. These findings provided further evidence that anticonvulsant osteomalacia results from hepatic enzyme induction which, by increasing the metabolism of cholecalciferol to inactive compounds, lowers 25-HCC levels in patients whose dietary vitamin D intake and exposure to sunlight are otherwise adequate. Results also indicated that under certain circumstances 25-HCC may have considerably stronger antirachitic potency in man than has hitherto been recognized.

Topics: Adolescent; Adult; Anticonvulsants; Binding, Competitive; Calcium; Child; Cholecalciferol; Diet; Enzyme Induction; Epilepsy; Female; Humans; Hydroxycholecalciferols; Liver; Male; Middle Aged; Osteomalacia; Phosphorus; Radioligand Assay; Rickets; Sunlight; Vitamin D

Topics: Adenylyl Cyclases; Anticonvulsants; Calcitonin; Calcium; Cholecalciferol; Cyclic AMP; Diagnosis, Differential; Humans; Hydroxycholecalciferols; Hypercalcemia; Hyperparathyroidism; Osteitis Deformans; Osteitis Fibrosa Cystica; Osteomalacia; Parathyroid Hormone; Pseudohypoparathyroidism; Radioimmunoassay; Thyroid Neoplasms

Topics: Animals; Anticonvulsants; Calcium; Calcium Isotopes; Carbon Isotopes; Cholecalciferol; Diuresis; Hydroxycholecalciferols; Kidney; Liver; Male; Osteomalacia; Phenobarbital; Phenytoin; Rats; Time Factors; Tritium; Whole-Body Counting

Topics: Adolescent; Adult; Aged; Carbon Isotopes; Cholecalciferol; Chromatography; Female; Humans; Kidney Failure, Chronic; Malabsorption Syndromes; Male; Middle Aged; Osteomalacia; Silicon Dioxide; Tritium; Vitamin D; Vitamin D Deficiency

Topics: Cholecalciferol; Follow-Up Studies; Growth; Growth Disorders; Humans; Long-Term Care; Osteomalacia; Phosphates; Rickets; Vitamin D

Topics: Carbon Isotopes; Cholecalciferol; Chromatography; Humans; Hypercalcemia; Nephrectomy; Osteomalacia; Sarcoidosis; Time Factors; Tritium; Vitamin D

Topics: Adult; Alcoholic Intoxication; Anti-Bacterial Agents; Bile Acids and Salts; Blind Loop Syndrome; Celiac Disease; Cholecalciferol; Chronic Disease; Feces; Humans; Intestinal Absorption; Intestinal Diseases; Intubation, Gastrointestinal; Jejunum; Malabsorption Syndromes; Male; Osteomalacia; Pancreatic Extracts; Pancreatitis; Tritium; Vitamin D Deficiency

Topics: Calcification, Physiologic; Cholecalciferol; Humans; Osteomalacia

Topics: Calcium; Cholecalciferol; Ergocalciferols; Humans; Hypoparathyroidism; Osteomalacia; Rickets; Vitamin D

Topics: Adolescent; Adult; Aged; Celiac Disease; Cholecalciferol; Female; Gastrectomy; Humans; Intestinal Absorption; Lipid Metabolism; Liver Cirrhosis; Malabsorption Syndromes; Male; Middle Aged; Osteomalacia; Pancreatitis; Protein-Losing Enteropathies; Rickets; Tritium; Vitamin D Deficiency

Isolation of the liver from the circulation of rats eliminates almost completely their ability to convert [1,2]-(3)H vitamin D(3) into its biologically active metabolite, 25-hydroxycholecalciferol, as well as certain other metabolites. It is concluded that the liver is the major if not the only physiologic site of hydroxylation of vitamin D(3) (cholecalciferol) into 25-hydroxycholecalciferol. The osteodystrophy and the higher requirements for vitamin D observed in hepatic insufficiencies may be due to an inability of the liver to transform vitamin D into its metabolically active form.

Topics: Animals; Cholecalciferol; Chromatography; Hepatectomy; Liver; Liver Diseases; Male; Osteomalacia; Osteoporosis; Rats; Rickets; Tritium; Vitamin D

Topics: Adult; Aged; Alkaline Phosphatase; Bone and Bones; Bone Development; Calcification, Physiologic; Calcium; Cholecalciferol; Female; Gastrectomy; Humans; Middle Aged; Osteomalacia; Phosphates; Postoperative Complications; Vitamin D Deficiency

Topics: Adolescent; Adult; Aged; Cholecalciferol; Female; Humans; Intestinal Absorption; Kidney Diseases; Liver Diseases; Malabsorption Syndromes; Male; Middle Aged; Osteomalacia; Tritium