vitamin-d-2 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

Topics: Biomarkers; Chromatography, High Pressure Liquid; Diagnosis, Differential; Ergocalciferols; Humans; Hypercalcemia; Hypocalcemia; Osteomalacia; Phosphorus Metabolism Disorders; Reference Values; Rickets; Specimen Handling; Vitamin D

Described herein is a case of oncogenic osteomalacia that ran a course of at least 16 years before curative resection of a mixed mesenchymal tumor. Hypercalcemic hyperparathyroidism developed in the patient, and review of the literature indicated that this occurs in about 10 percent of reported cases. Changes in serum parathyroid hormone levels with and without phosphate supplement therapy and before and after tumor resection suggested that both the high intake of phosphate and the effect of the neoplasm on vitamin D bioactivation engendered the parathyroid overactivity. Despite marked hyperparathyroidism, serum 1,25-dihydroxyvitamin D levels were subnormal preoperatively but showed a sevenfold increase within 48 hours of tumor resection. Thereafter, a gradual increase in the maximal tubular reabsorption of phosphate occurred during several months. Biopsy of the iliac crest confirmed that tumor removal was followed by resolution of osteomalacia, but there was no accompanying increase in vertebral mineral density as assessed by quantitative computed tomography or in total-body bone mineral as measured with dual-photon absorptiometry. The findings presented are consistent with secretion by the tumor of a factor with a short half-life that is potent enough to inhibit renal 25-hydroxyvitamin D-1 alpha-hydroxylase despite hyperparathyroidism. The resulting subnormal circulating 1,25-dihydroxyvitamin D levels may have secondarily contributed to decreased renal tubular reabsorption of phosphate.

Topics: Chronic Disease; Combined Modality Therapy; Dihydroxycholecalciferols; Ergocalciferols; Female; Homeostasis; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Mesenchymoma; Middle Aged; Osteomalacia; Phosphates; Soft Tissue Neoplasms

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

The effect of 1 alpha OHD2 and 1 alpha OHD3 have been studied in rachitic, normal, and prednisolone-treated male rats. The healing of rickets, the stimulation of intestinal Ca and P transport, the effect on bone mineral, and the induction of renal calcifications have been examined. The two 1-hydroxylated compounds are equally potent in healing rickets, and by comparison with previous data are equivalent to 100-200 IU/micrograms. 1 alpha OHD2 and 1 alpha OHD3 stimulated intestinal Ca and P transport to the same extent and were antagonistic to prednisolone in this respect. 1 alpha OHD2 reduced the number of osteoclasts and increased bone mineral in normal rats in contrast to 1 alpha OHD3, which increased osteoclasts and slightly reduced bone mineral. Prednisolone-induced osteopenia was more effectively counteracted by 1 alpha OHD2 than by 1 alpha OHD3. Mortality rate was higher in rats intoxicated with 1 alpha OHD3 than for rats given 1 alpha OHD2. LD50 was estimated to be five to fifteen times higher for 1 alpha OHD2. Renal calcification were more pronounced after dosing with 1 alpha OHD3 than after treatment with 1 alpha OHD2. When prednisolone was given together with 1 alpha OHD2 or 1 alpha OHD3, renal calcifications were further increased. These observations demonstrate physiological dissimilarities between vitamin D2 and vitamin D3 in rats which are in accordance with a different metabolism of the two vitamins. The findings, in particular that 1 alpha OHD2 is less toxic than 1 alpha OHD3, are of potential clinical importance.

Topics: Animals; Biological Transport; Bone and Bones; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Humans; Hydroxycholecalciferols; Hypoparathyroidism; Intestinal Absorption; Intestines; Kidney; Liver; Osteomalacia; Osteoporosis; Phosphorus; Prednisolone; Rats; Rickets; Skin; Vitamin D

Topics: 25-Hydroxyvitamin D 2; Adolescent; Aged; Animals; Calcitriol; Chemical Phenomena; Chemistry; Dehydrocholesterols; Ergocalciferols; Female; Humans; Infant; Osteomalacia; Pregnancy; Rats; Rickets; Ultraviolet Rays; 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

Topics: Adolescent; Adult; Alkaline Phosphatase; Asia; Calcium; Clinical Enzyme Tests; England; Ergocalciferols; Female; Humans; Hypercalcemia; Hypocalcemia; Male; Osteomalacia; Parathyroid Glands; Parathyroid Hormone; Pregnancy; Pregnancy Complications; Rickets; 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: Bone Diseases; Calcinosis; Chronic Kidney Disease-Mineral and Bone Disorder; Diet Therapy; Ergocalciferols; Fibrous Dysplasia of Bone; Fractures, Spontaneous; Humans; Hyperparathyroidism, Secondary; Hypocalcemia; Kidney Transplantation; Metabolic Diseases; Osteomalacia; Osteosclerosis; Parathyroid Glands; Phosphates; Renal Dialysis; Tendon Injuries; Vitamin D

Topics: Adult; Animals; Calcium Metabolism Disorders; Child; Child, Preschool; Developing Countries; Ergocalciferols; Ergosterol; Fish Oils; Humans; Infant; Osteomalacia; Phosphorus; Rickets; Sunlight; Vitamin D Deficiency

Bone disease with osteoporosis and osteomalacia are common in sickle cell disease (SCD). Some patients have vitamin D deficiency and low bone mineral density (BMD). The role of vitamin D and calcium supplementation to restore bone health in SCD has not been well studied. In 14 adults with SCD, we measured 25(OH)D (25-hydroxyvitamin D) and BMD at the femoral neck, lumbar spine, and distal third of the ulna plus radius, along with markers of bone resorption (CTx; C-terminal component of pro-collagen type I) and bone formation (osteocalcin) before and after 12 months of vitamin D(2) and calcium carbonate treatment. Pretreatment, all patients were vitamin D deficient with a mean 25(OH)D level of 11.6 [corrected] +/- 4 [corrected] ng/ml, had low BMD at the lumbar spine (L-spine), 0.87 +/- 0.11 g/cm(2) (mean Z-score of -2.6 3 +/- 0.71 SD and T score of -2.31 +/- 0.75 SD), femoral neck, 0.8 +/- 0.18 g/cm(2) (mean Z-score -1.36 +/- 0.84, T-score -1.14 +/- 0.75), and the distal radius and ulna, 0.6 +/- 0.17 g/cm(2) (mean Z-score -1.18 +/- 0.79, T-score -1.01 +/- 0.74) and had elevated CTx (0.87 +/- 0.5 ng/ml) and osteocalcin levels (12.3 +/- 3.7 ng/mul). After treatment, all patients corrected their 25(OH)D level (34.6 [corrected] +/- 11 [corrected] ng/ml) (P < 0.001) with a 3.6% +/- 3.9% increase in BMD at the L-spine (P = 0.009), 4.6% +/- 8.5% increase at the femoral neck (P = 0.05) and 6.5% +/- 12.6% increase at the distal radius plus ulna (P = 0.09). CTx, osteocalcin, and PTH(i) levels were unchanged. Treatment of adult SCD with vitamin D and calcium can restore 25(OH)D levels to normal and improve BMD, but, markers of bone resorption remained unchanged. Screening for vitamin D deficiency and BMD in SCD patients seems warranted.

Topics: Adult; Anemia, Sickle Cell; Bone Density; Bone Resorption; Calcium Carbonate; Collagen Type I; Drug Therapy, Combination; Ergocalciferols; Femur Neck; Humans; Lumbar Vertebrae; Osteocalcin; Osteomalacia; Osteoporosis; Parathyroid Hormone; Peptides; Pilot Projects; Vitamin D; Vitamin D Deficiency

Forty one elderly patients admitted to hospital for acute illnesses were also found to have subclinical osteomalacia. Immediately before discharge, therefore, all were randomised to receive either vitamin D2 25 micrograms daily, alfacalcidol 0.5 micrograms daily, or placebo. Treatment was given for at least three months, those allocated to placebo then being switched to an active drug. Within the first three months of treatment with either of the active drugs most patients had exhibited a fall to normal in osteoid values. In only four treatment periods was there a mild increase in serum calcium concentration, and in no patient was this accompanied by deterioration in renal function. Any increase in serum creatinine concentration was invariably attributable to the underlying disease for which the patient had been admitted in the first place. Subclinical osteomalacia in the elderly may be corrected by relatively low doses of alfacalcidol (0.5 micrograms daily) or vitamin D2 (25 micrograms daily) given for three months. Such treatment is safe and not accompanied by a serious risk of hypercalcaemia or renal impairment.

Topics: Aged; Calcium; Clinical Trials as Topic; Creatinine; Ergocalciferols; Humans; Hydroxycholecalciferols; Osteomalacia; Random Allocation

Although osteomalacia is known to be common in some sections of the elderly population, the disease is often subclinical and there is uncertainty about the point at which treatment is necessary. Identification and treatment of osteomalacia are inseparably bound; the response of varying degrees of subclinical disease to treatment with vitamin D or alfacalcidol is described here. The response is assessed in relation to a simply derived reference range based on standard biochemical measurements together with a Jamshidi needle biopsy of the iliac crest. Although this technique does not define a truly normal range it identifies a treatable abnormality which could form the basis of further study of the problem of subclinical osteomalacia in the elderly.

Topics: Aged; Biopsy; Bone and Bones; Clinical Trials as Topic; Ergocalciferols; Humans; Hydroxycholecalciferols; Osteomalacia

Different methods for the prevention and treatment of vitamin D deficiency were studied in 42 institutionalized elderly people. One group received ultraviolet radiation (UVR) on a large area of the body surface once a week for three months. The results were compared with those in groups receiving either 450 IU vitamin D2 together with 420 mg calcium daily, 420 mg calcium alone, or no treatment. A significant increase in serum 25-hydroxyvitamin D was obtained with UVR. A similar increase was obtained with oral vitamin D2. A small but significant decrease in serum alkaline phosphatase was observed in subjects receiving vitamin D and calcium or calcium alone. No effects on serum phosphate, urinary cyclic adenosine monophosphate and urinary calcium were seen. Though brief UVR at one-week intervals is an efficient and safe method for prevention of vitamin D deficiency in the elderly, it is in our experience time-consuming for the ward staff and thus less convenient than oral vitamin D supplementation.

Topics: Administration, Oral; Age Factors; Aged; Alkaline Phosphatase; Calcifediol; Calcium; Ergocalciferols; Homes for the Aged; Humans; Osteomalacia; Ultraviolet Therapy; Vitamin D Deficiency

Topics: Adult; Aged; Anticonvulsants; Bone and Bones; Calcium; Clinical Trials as Topic; Ergocalciferols; Humans; Middle Aged; Minerals; Osteomalacia

Vitamin D (vitD) deficiency and bone loss may occur after bariatric surgery and hence, supplementation with high oral doses of vitD may be required. Alternatively, intramuscular depot ergocalciferol, which slowly releases vitD and bypasses the gastrointestinal tract, could be administrated. We present a case of severe vitD deficiency-osteomalacia after gastric bypass operation for morbid obesity, treated with ergocalciferol intramuscularly. A 45-year-old woman was presented with hip pain and muscle weakness, which led ultimately to immobilization in a wheelchair. Fifteen years ago, she underwent roux-en-Y gastric by-pass for morbid obesity. Occasionally, she was treated with multivitamin supplements. On admission, iron deficiency anaemia, vitD deficiency (25OHD: 3.7 ng/ml) and secondary hyperparathyroidism were revealed. Bone turnover markers (BTM) were elevated. Radiological evaluation demonstrated insufficiency fractures on the pubic and left femur and reduced BMD. Osteomalacia due to vitD deficiency and calcium malabsorption were diagnosed. Calcium citrate 500 mg qid and intramuscular ergocalciferol 600,000 IU every 20 days were initiated. One month later, musculoskeletal pain and weakness were resolved and the patient was mobilized. Few months later, vitD, BTM and BMD showed substantial improvement. Intramuscular ergocalciferol administration can improve the clinical and biochemical status and thus, is suggested to prevent and/or treat osteomalacia in such patients.

Topics: Bone Density Conservation Agents; Delayed-Action Preparations; Ergocalciferols; Female; Fractures, Stress; Gastric Bypass; Humans; Injections, Intramuscular; Middle Aged; Obesity, Morbid; Osteomalacia; Vitamin D Deficiency

N-terminal propeptide of type I procollagen (PINP) is a marker of newly formed type I collagen. However, its role in hypophosphatemic rickets/osteomalacia has not yet been established. Metabolic bone markers were examined in patients with oncogenic osteomalacia (OOM) and X-linked hypophosphatemic rickets (XLH), and in healthy controls. OOM and XLH patients were found to have hypophosphatemia secondary to elevated levels of serum fibroblast growth factor 23 (FGF-23). OOM patients had reduced levels of 1,25-dihydroxy vitamin D (1,25D) compared with XLH patients and healthy controls, despite attenuation of the reduction in these levels in the XLH patients secondary to active vitamin D supplementation. In contrast to patients with XLH, OOM patients showed a significant increase in serum PINP, which is suggestive of accelerated bone matrix formation. Bone alkaline phosphatase (BAP) and the BAP/PINP ratio were also increased in OOM but not in XLH patients, suggesting the presence of a disturbance in bone mineralization in OOM. Long-term supplementation of active form vitamin D and inorganic phosphate (IP) may have attenuated the defect in bone mineralization in the XLH patients, resulting in the normalization of PINP, BAP, and the BAP/PINP ratio. The present results suggest that, as with BAP, PINP is an appropriate metabolic bone marker in the assessment of hypophosphatemic rickets/osteomalacia.

Topics: Adult; Alkaline Phosphatase; Biomarkers; Biomarkers, Tumor; Bone and Bones; Calcitriol; Ergocalciferols; Familial Hypophosphatemic Rickets; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Genetic Diseases, X-Linked; Humans; Male; Middle Aged; Neoplasms, Connective Tissue; Osteomalacia; Paraneoplastic Syndromes; Peptide Fragments; Procollagen

Kidney disease patients experience declining calcitriol levels and develop secondary hyperparathyroidism (SHPT). Animal models of uremia based on 5/6 nephrectomy (NTX) do not consistently reproduce this calcitriol deficiency. We developed an animal model, the NTX Cyp27b1-null mouse, which completely lacks endogenous calcitriol, and examined the suitability of this model for evaluation of treatment with vitamin D analogs in uremia.. NTX was performed at 2 months of age. One week post-NTX, animals were treated for 4 weeks with vehicle; doxercalciferol at 30, 100 or 300 pg/g body weight (b.w.); or paricalcitol at 100, 300 or 1,000 pg/g b.w. by gavage 3 times per week.. Serum blood urea nitrogen and creatinine were elevated. Vehicle-treated NTX null mice had hypocalcemia and SHPT. Doxercalciferol at 100 or 300 pg/g b.w. normalized serum calcium and parathyroid hormone (PTH) levels. Paricalcitol at 300 or 1,000 pg/g normalized serum calcium, but PTH levels remained elevated. Osteomalacia was corrected by 100 pg/g b.w. of doxercalciferol or 1,000 pg/g b.w. of paricalcitol. The highest dose of doxercalciferol, but not of paricalcitol, significantly reduced osteitis fibrosa.. Our results reveal the differential efficacy of doxercalciferol and paricalcitol in this novel animal model incorporating both calcitriol deficiency and renal insufficiency.

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Administration, Oral; Animals; Calcitriol; Calcium; Disease Models, Animal; Dose-Response Relationship, Drug; Ergocalciferols; Mice; Mice, Knockout; Osteitis; Osteomalacia; Parathyroid Hormone; Uremia

Hypovitaminosis D and its consequences are significant complications in the course of untreated celiac disease (CD). We report a case that illustrates the natural evolution of osteomalacia in an adult patient with untreated CD and his response to vitamin D supplementation. In patients with complicated CD and hypovitaminosis D, vitamin D-2 replacement in high enough doses is important to improving functional performance and for the treatment of osteomalacia.

Topics: Calcium; Celiac Disease; Diet, Gluten-Free; Dose-Response Relationship, Drug; Ergocalciferols; Humans; Lumbar Vertebrae; Male; Middle Aged; Osteomalacia; Osteoporosis; Radiography; Spinal Diseases; Sternum; Thoracic Vertebrae; Vitamin D Deficiency

A 17-year-old Filipino male hemodialysis patient presented for renal transplant evaluation. He had significant skeletal abnormalities characterized by bone pain, an inability to walk, and secondary hyperparathyroidism despite therapy with an active vitamin D sterol (paricalcitol).. The patient underwent a physical examination, and his serum levels of calcium, phosphorus, alkaline phosphatase, parathyroid hormone, aluminum and 25-hydroxycholecalciferol (25OH-vitamin D) were determined. X-rays of hips and lower extremities, MRI, and bone histomorphometry after double tetracycline labeling were performed.. Osteomalacia associated with low 25OH-vitamin D levels.. Monthly therapy with ergocalciferol (vitamin D2) and discontinuation of paricalcitol.

Topics: Adolescent; Bone Density Conservation Agents; Ergocalciferols; Follow-Up Studies; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Male; Osteomalacia; Renal Dialysis; Vitamin D Deficiency

Topics: 25-Hydroxyvitamin D 2; Absorptiometry, Photon; Aged; Alendronate; Alkaline Phosphatase; Back Pain; Bone Density; Calcium; Ergocalciferols; Female; Humans; Lumbar Vertebrae; Osteomalacia; Osteoporosis, Postmenopausal; Treatment Outcome

A high incidence of long-bone fractures has been observed in children and young adults with quadriplegic cerebral palsy in residential care. This study aimed to determine factors that contribute to these fractures and to institute preventive treatment. Twenty individuals (12 males, eight females) of a cohort of 88 residents with spastic quadriplegia in residential care in Gauteng, South Africa who had sustained fractures were compared with a random sample of age-matched control participants (10 males, 10 females) from the same facility. Participants ranged in age from 6 to 29 years (median 17.5 years). The majority of fractures were in the upper extremities. There was radiological and biochemical evidence of rickets and osteomalacia in both groups. However, the severity of the disease was more pronounced in the group with fractures. There was a significant relation (p=0.002) between the number of fractures and the use of anticonvulsant therapy (ACT). Three months of vitamin D administration (calciferol 5000 iu/day) resulted in a marked clinical improvement. There were no fractures during this period in either group. In addition, the mean serum calcium (Ca) and phosphate (Pi) levels increased (Ca from 2.17 to 2.35 mmol/L and Pi from 1.13 to 1.66 mmol/L) and mean total alkaline phosphatase level decreased (from 1123 to 423 U/L). We concluded that vitamin D deficiency was the major factor contributing to the occurrence of fractures in this population. Unless sunlight exposure can be guaranteed, vitamin D supplementation should be considered for children and adults in residential care, especially if they are on ACT, even in areas with year-round sunshine.

Topics: Adolescent; Alkaline Phosphatase; Anticonvulsants; Calcium; Cerebral Palsy; Child; Cohort Studies; Ergocalciferols; Femoral Fractures; Humans; Incidence; Light; Long-Term Care; Nutritional Status; Osteomalacia; Prevalence; Radiography; Rickets; Seizures; Severity of Illness Index; South Africa; Vitamin D Deficiency

A 60-year-old man with portal hypertensive gastropathy due to type C liver cirrhosis developed severe bone pains, marked hypophosphatemia with inappropriately increased urinary excretion of phosphate (%TRP; 9.6%), and hyperalkaline phosphatasia, after intravenous administration of saccharated ferric oxide (SFO) at a dose of 80-240 mg/week over a period of more than 5 years. The total iron infused was estimated to be more than 25 g. On a diagnosis of SFO-induced osteomalacia, the infusion of iron was immediately discontinued, and phosphate and vitamin D2 (1000 IU/day) were administered. Serum levels of 25-OHD2 increased after 1 week, whereas levels of 1,25-(OH)2D2 did not increase until 3 months later, accompanied by improvement of renal tubular reabsorption of phosphate and gradual improvement of the bone pains. The patient has been doing well for the last 2 years, with normal serum levels of phosphate, calcium, and alkaline phosphatase, without any supplementation of phosphate, vitamin D, or iron-containing agents. In primary culture of neonatal mouse renal tubules, in which 1,25-(OH)2D3 was produced from 25-OHD3 in response to PTH, SFO significantly inhibited PTH-induced production of 1,25-(OH)2D3 at 30 mumol/L, which is attainable in the urine of patients receiving a therapeutic intravenous dose of SFO. Furthermore, SFO decreased the calcium content and inhibited 45Ca incorporation in cultured fetal mouse parietal bones at 3 mumol/L. Such SFO concentration may be transiently observed in the plasma of patients receiving excessive intravenous doses of SFO for a prolonged period. These in vitro findings together with the clinical observations suggest that SFO, after filtration through the glomerulus and reabsorption in the proximal renal tubules, impaired proximal renal tubular function, such as tubular reabsorption of phosphate and 1 alpha-hydroxylase activity, leading to hypophosphatemic osteomalacia. Furthermore, it is highly likely that SFO in the peripheral blood, when transferrin is saturated with iron, may impair bone formation and aggravate osteomalacia. Although SFO-induced osteomalacia is reversible simply by discontinuation of the agent, excessive and prolonged administration of SFO should be avoided.

Topics: Alkaline Phosphatase; Animals; Bone Development; Calcitriol; Calcium; Dose-Response Relationship, Drug; Ergocalciferols; Ferric Compounds; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Hypophosphatemia; Injections, Intravenous; Kidney Tubules; Liver Cirrhosis; Male; Mice; Middle Aged; Osteomalacia; Pain; Parathyroid Hormone; Parietal Bone; Phosphates

Renal osteodystrophy improves after renal transplantation but, after the procedure, other forms of bone disease emerge. We report a male patient that received a renal allograft four years before, who consulted for low back pain secondary to multiple vertebral compression fractures. The patient had good renal function, a parathormone independent hyperphosphaturia, normal 25-OH cholecalciferol, increased urinary hydroxyproline, decreased osteocalcin, reduced bone density and a bone biopsy revealing osteomalacia. The diagnosis of hypophosphatemic osteomalacia was reached and treatment with phosphates and ergocalciferol was started but, despite this, the patient suffered a new fracture two years later. Two mechanisms can produce hypophosphatemia after a renal transplantation: a parathormone excess due to the previous renal failure, that disappears during the first year after the transplantation or a derangement in renal phosphate transport that can be due to a generalized proximal tubule solute transport derangement (Fanconi syndrome), parathormone hypersensitivity or to an "idiopathic" hyperphosphaturia. Despite a good treatment, bone mass is not recovered and there is a high fracture risk. Mineral metabolism must be closely monitored after a renal allograft and its alterations must be quickly treated.

Topics: Adult; Ergocalciferols; Humans; Kidney Transplantation; Male; Osteomalacia; Osteoporosis; Phosphates; Severity of Illness Index

Topics: Adolescent; Adult; Bone Density; Calcium; Ergocalciferols; Female; Humans; Magnesium; Male; Middle Aged; Osteomalacia; Osteoporosis; Phosphorus; Tetany

Topics: Absorptiometry, Photon; Adult; Aged; Bone Density; Calcium; Ergocalciferols; Female; Humans; Lumbar Vertebrae; Male; Middle Aged; Osteomalacia; Prognosis

Bone disease with total parenteral nutrition (TPN) has been attributed to aluminum loading or vitamin D therapy. We studied 17 patients who first received TPN containing casein hydrolysate with high Al and ergocalciferol (25 micrograms/d) for 6-72 mo followed by TPN containing amino acids with reduced Al and ergocalciferol (5 micrograms/d) for 9-58 mo. We also did a cross-sectional study of 22 patients receiving casein and ergocalciferol (25 micrograms/d) compared with 46 patients receiving amino acids and ergocalciferol (5 micrograms/d) for 6-58 mo. Bone formation was higher and osteoid area, bone-surface stainable Al and total bone Al were lower with amino acid TPN than with casein TPN. Bone formation varied inversely with both plasma Al and bone-surface Al, suggesting that plasma or bone-surface Al, acquired during TPN, can reduce bone formation and lead to patchy osteomalacia. Serum levels of iPTH and 1,25-dihydroxyvitamin D were higher with amino acid TPN.

Topics: Aluminum; Amino Acids; Bone and Bones; Bone Development; Bone Diseases, Metabolic; Calcium; Caseins; Creatinine; Ergocalciferols; Humans; Metabolic Clearance Rate; Osteomalacia; Parenteral Nutrition, Total; Protein Hydrolysates

We surveyed calcidiol levels (25-OH-D) in a geographically-defined population of 373 women, ages 20-80 yr to test for an association between occult osteomalacia and excess bone loss. Bone mass was measured by photon densitometry and an estimate of vitamin D was determined by measuring dietary and supplemental intake as well as sunlight exposure equivalent. The relationship of smoking practices, alcohol use, exogenous estrogen use, and medications to calcidiol level was assessed. Calcidiol levels were not associated with bone mass levels observed at two different forearm sites. Low levels of calcidiol, indicative of generalized vitamin D deficiency, were not observed in this population though mean estimates of vitamin D intakes from food 119 +/- 148 IU) or food and supplements (319 +/- 463 IU) were less than the Recommended Dietary Allowance (400 IU). Calcidiol was significantly associated with estimates of vitamin D intake from food (r = 0.11), supplement use (r = 0.21), and sunlight equivalent exposure (r = 0.26). Calcidiol levels were negatively related to age (p = 0.0020) and positively related to exogenous estrogen use and premenopausal state independent of age.

Topics: 25-Hydroxyvitamin D 2; Adult; Aged; Aging; Bone and Bones; Contraceptives, Oral, Hormonal; Cross-Sectional Studies; Diet; Ergocalciferols; Female; Humans; Iowa; Menopause; Middle Aged; Minerals; Osteomalacia; Smoking; Sunlight; Vitamin D

A patient received 2.5 mg vitamin D2 daily for 10 years and presented with increasing skeletal pain and hypercalcaemia. The limbs were painful to touch especially at the insertions of ligaments and tendons, and radiographs showed osteosclerosis with calcification in the periosteum, blood vessels, tendoachilles and plantar fascia. Bone histomorphometry showed increased amounts of osteoid and defective mineralisation despite hypercalcaemia, hyperphosphataemia and raised serum concentrations of vitamin D metabolites. A negative external calcium balance was documented in the presence of enhanced intestinal calcium absorption and an increase in urinary hydroxyproline excretion. Cortisone improved calcium balance and corrected the hypercalcaemia by reducing serum 1,25-dihydroxyvitamin D levels and urinary hydroxyproline excretion.

Topics: Bone and Bones; Calcium; Ergocalciferols; Female; Humans; Hypercalcemia; Middle Aged; Osteomalacia; Syndrome; Vitamin D

A 25-yr-old black man with cystic fibrosis and cirrhosis developed symptoms of osteomalacia and hypocalcemia, hypophosphatemia, secondary hyperparathyroidism, and low circulating 25-hydroxyvitamin D (25-OHD). Serum 1,25-dihydroxyvitamin D (1,25-[OH]2D) was within the normal range. Iliac crest bone biopsy confirmed the diagnosis of osteomalacia. Oral administration of 50,000 IU of vitamin D2 failed to relieve symptoms or raise serum 25-OHD levels to normal. Intramuscular vitamin D2, 10,000 IU every 8-12 week, improved symptoms, raised serum 25-OHD to normal, and increased circulating 1,25-[OH]2D to values five times normal. Over the next 10 mo circulating 1,25-[OH]2D remained elevated despite normalization of serum calcium, phosphorus, and parathyroid hormone. Repeat bone biopsy 1 yr after parenteral vitamin D showed healing of the osteomalacia. Malabsorption of vitamin D appears secondary to profound steatorrhea due to pancreatic insufficiency and secondary biliary cirrhosis. Although extensive hepatocellular disease was present, hepatic conversion of vitamin D to 25-OHD was intact. Both high and low circulating 1,25-[OH]2D levels during active osteomalacia have been reported; initially, the level was in the normal range and higher values in this patient occurred with repletion of 25-OHD substrate. This study shows that symptomatic osteomalacia may be a major manifestation of cystic fibrosis in those patients surviving into adulthood. Measurements of serum 25-OHD in cystic fibrosis patients may identify those who should receive supplemental vitamin D.

Topics: Adult; Bone and Bones; Calcium; Cystic Fibrosis; Ergocalciferols; Humans; Hydroxycholecalciferols; Hyperparathyroidism, Secondary; Hypocalcemia; Liver; Liver Cirrhosis; Magnesium; Malabsorption Syndromes; Male; Osteomalacia; Parathyroid Hormone; Phosphorus; Serum Albumin; Vitamin D

On the basis of two recent clinical cases seen in immigrants, the authors review osteomalacia and its relationship with childhood rickets. They demonstrate that treatment with a combination of calcium and vitamin D readily halts the progression of the disease during pregnancy; the major problem therefore consists of making the diagnosis.

Topics: Adult; Calcium; Ergocalciferols; Female; Humans; Osteomalacia; Pregnancy; Pregnancy Complications

An investigation into plasma calcium concentrations and the biochemical factors which regulate it in vegetarian Asian subjects without clinical or radiological features of osteomalacia revealed the presence of low serum 25-hydroxyvitamin D concentrations and elevated PTH concentrations, even in the presence of calcium levels in the normal range (up to 2.35 mmol/liter). These elevated PTH concentrations, though not as high as those in osteomalacic patients with hypocalcemia, often persisted despite treatment with vitamin D, normalization of 25-hydroxyvitamin D, and an increase in calcium concentrations. In one patient the PTH concentration remained high even when the plasma calcium concentration became supranormal. Therefore, secondary hyperparathyroidism is commonly associated with vegetarianism, and may play an important role in maintaining calcium concentrations within the normal range. Persistent elevation of PTH despite normalization of 25-hydroxyvitamin D also points to autonomous PTH hypersecretion, which may result in osteolysis in the long term, and raises the question of the need for vitamin D supplementation in vegetarians with low dietary intake of vitamin D.

Topics: 25-Hydroxyvitamin D 2; Asia; Calcifediol; Calcium; Diet, Vegetarian; Ergocalciferols; Humans; Osteomalacia; Parathyroid Hormone; Rickets; Vitamin D

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

Topics: Adult; Ergocalciferols; Female; Humans; Male; Osteomalacia; Phosphates; Rickets

A 48-year-old woman underwent jejunoileal bypass surgery for obesity while hypercalcemic. Three years later, she developed symptomatic osteomalacia impairing her daily activities. Bone biopsy confirmed the clinical diagnosis of osteomalacia, and treatment with 8000 U daily of vitamin D and milk resulted in striking improvement of clinical symptoms and resolution of her osteomalacia both chemically and histologically. The patient, however, again became hypercalcemic and a parathyroid adenoma was subsequently removed with restoration of serum calcium values to normal. Neither the occurrence and successful treatment of gross symptomatic osteomalacia consequent to jejunoileal bypass surgery, nor the obscuration of primary hyperparathyroidism by osteomalacia has been hitherto well documented in the United States.

Topics: 25-Hydroxyvitamin D 2; Biopsy; Bone and Bones; Dihydroxycholecalciferols; Ergocalciferols; Female; Humans; Hyperparathyroidism; Ileum; Jejunum; Middle Aged; Obesity; Osteomalacia; Postoperative Complications; Vitamin D

Topics: Adolescent; Adult; Aged; Bone and Bones; Calcifediol; Calcitriol; Calcium; Ergocalciferols; Female; Humans; Hydroxycholecalciferols; Hypophosphatemia, Familial; Male; Middle Aged; Osteomalacia; Parathyroid Hormone; Phosphorus; Rickets; X Chromosome

Topics: 24,25-Dihydroxyvitamin D 3; Calcifediol; Calcitriol; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydroxycholecalciferols; Ergocalciferols; Humans; Hydroxycholecalciferols; Hypoparathyroidism; Intestinal Absorption; Osteomalacia; Osteoporosis; Rickets; Tetany; Vitamin D

Twenty-nine patients with chronic liver disease, nine of whom had symptoms suggesting bone disease, were studied by bone histology. Nine had osteomalacia; six associated with cholestatic liver disease and three with primarily hepatocellular disease. Two of these had clinical and biochemical features of cholestasis for at least a year and the other had alcoholic cirrhosis associated with severe malnutrition. Excluding the latter patient, histological osteomalacia was significantly associated with presence and duration of cholestasis. Plasma 25-hydroxyvitamin D was low and fasting urine hydroxyproline/creatinine ratio was high in all patients with osteomalacia but were abnormal also in some patients who did not have histological osteomalacia. Serum calcium, phosphate, alkaline phosphatase, vitamin D-binding protein and radiology were unhelpful in many patients with osteomalacia. Vitamin D-deficiency correlated significantly with deficiency of other fat-soluble vitamins and those patients with rachitic levels of plasma 25-hydroxyvitamin D showed no seasonal variation, suggesting a combination of malabsorption of vitamin D and reduced sunlight exposure. We suggest that patients with chronic liver disease with cholestasis for at least a year are at risk from osteomalacia and that those likely to have this complication may be identified by plasma 25-hydroxyvitamin D and/or fasting urine hydroxyproline/creatinine ratio measurements. The diagnosis can only be made with certainty by bone biopsy.

Topics: 25-Hydroxyvitamin D 2; Adolescent; Adult; Aged; Cholestasis; Chronic Disease; Ergocalciferols; Humans; Liver Diseases; Middle Aged; Osteomalacia; Risk; Seasons; Vitamin D Deficiency

Vitamin D metabolites were measured in 21 patients with hypophosphatemic osteomalacia of juvenile onset. In eight patients who had not received any antirachitic treatment, serum 25-hydroxyvitamin D(25-OH-D) and 1,25-dihydroxyvitamin D (1,25-[OH]2D) values were normal, whereas serum 24,25-dihydroxyvitamin D (24,25-[OH]2D) values were lower than in normal subjects. In 13 patients who were receiving ergocalciferol and oral elemental phosphorus, serum 25-OH-D and 24,25-(OH)2D concentrations were elevated and serum 1,25-(OH)2D values were low. The findings in untreated patients supported the hypothesis that vitamin D metabolism is abnormal in hypophosphatemic rickets/osteomalacia. The reduction of serum 1,25-(OH)2D levels with ergocalciferol and phosphate therapy gives further support to a therapeutic role for 1,25-(OH)2D in this disorder.

Topics: 24,25-Dihydroxyvitamin D 3; Adolescent; Adult; Aged; Alkaline Phosphatase; Calcifediol; Calcitriol; Child; Child, Preschool; Dihydroxycholecalciferols; Ergocalciferols; Female; Humans; Male; Middle Aged; Osteomalacia; Parathyroid Hormone; Phosphates; Phosphorus; Rickets; Vitamin D

The prevalence of vitamin D deficiency in Crohn's disease and the relationship of vitamin D status to metabolic bone disease have not been fully characterized. Serum 25-hydroxyvitamin D was measured in 82 patients with Crohn's disease; 65% of Crohn's disease patients had a low serum 25-hydroxyvitamin D concentration; 25% had deficient levels (less than 10 ng/ml). The lowest 25-hydroxyvitamin D levels were observed in patients with previous ileal resections. Nine patients were studied in detail including transiliac needle bone biopsies; 6 had osteomalacia and 3 osteoporosis. Six patients had repeat bone biopsies 9 to 18 mo after vitamin D treatment. Three patients with osteomalacia and low serum 25-hydroxyvitamin D levels showed histologic improvement after therapy with oral vitamin D restored serum 25-hydroxyvitamin D levels to normal. The adequacy of therapy was assessed accurately by monitoring serum 25-hydroxyvitamin D concentration. Three patients with metabolic bone disease with normal serum 25-hydroxyvitamin D levels at diagnosis did not show histologic improvement after receiving vitamin D.

Topics: 25-Hydroxyvitamin D 2; Adult; Aged; Bone and Bones; Bone Diseases, Metabolic; Crohn Disease; Ergocalciferols; Female; Humans; Male; Middle Aged; Osteomalacia; Vitamin D; Vitamin D Deficiency

The efficacy of vitamin D2 in the dose of 2000 IU daily in reversing anticonvulsant osteomalacia was studied in nine epileptic inpatients. The treatment with vitamin D2 was associated with increased serum 25-hydroxycalciferol and 24,25-dihydroxyvitamin D concentrations and partial healing of osteomalacic changes in the cancellous bone of the iliac crest. But it was concluded that the dose of vitamin D2, 2000 IU daily, was too small and that calcium supplementation may be needed in addition to vitamin D therapy.

Topics: 24,25-Dihydroxyvitamin D 3; Adult; Alkaline Phosphatase; Anticonvulsants; Bone and Bones; Calcifediol; Calcium; Dihydroxycholecalciferols; Epilepsy; Ergocalciferols; Female; Humans; Male; Middle Aged; Osteomalacia; Phosphates

Topics: Adult; Child; Ergocalciferols; Humans; Infant, Newborn; Osteomalacia; Rickets; 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

Previous reports have suggested that secondary hyperparathyroidism is extremely uncommon in hepatic osteomalacia. This, together with other findings, has led to suggestions that in chronic liver disease there may be selective resistance of bone to vitamin D or a specific bone mineralization defect unrelated to Vitamin D. To examine these possibilities, twenty-five patients with chronic liver disease have been studied by bone biopsy, serum calcium and inorganic phosphate, plasma 25-hydroxyvitamin D, plasma immunoreactive parathormone (iPTH), fasting urine cAMP, fasting renal tubular maximal reabsorptive capacity for phosphate (TmP/GFR) and fine grain hand x-rays. Nine of the patients had osteomalacia on bone biopsy, eight of these had subnormal levels of plasma 25-hydroxyvitamin D and the other had a borderline result. Based on the consensus of all the tests, five of these had evidence of secondary hyperparathyroidism. Plasma iPTH was higher in patients with osteomalacia than in patients without osteomalacia (P less than 0.01) or controls (P less than 0.01). Urine cAMP was higher in patients with osteomalacia than in patients without osteomalacia (P less than 0.001) or controls (P less than 0.01). TmP/GFR was significantly lower in patients with osteomalacia than in controls (P less than 0.05) but not significantly different from patients without osteomalacia. The findings of this study indicate that hyperparathyroidism occurs in a substantial proportion of patients with the osteomalacia of chronic liver disease. Moreover, osteomalacia in chronic liver disease is clearly related to reduced levels of plasma 25-hydroxyvitamin D. We conclude that hepatic osteomalacia is a vitamin D deficiency state and there is no need to suggest an unusual aetiology.

Topics: 25-Hydroxyvitamin D 2; Chronic Disease; Cyclic AMP; Ergocalciferols; Humans; Hyperparathyroidism, Secondary; Liver Diseases; Osteomalacia; Parathyroid Hormone

Patients receiving long term parenteral nutrition may develop metabolic bone disease. In all 11 patients studied, histologic studies of bone showed excessive unmineralized bone tissue despite normal plasma 25-hydroxyvitamin D levels. Three patients also had bone pain and fractures and severe urinary loss of calcium and phosphate. Withdrawal of vitamin D from parenteral nutrition solutions was associated with improved histologic findings of bone in all patients, shown by a decrease in osteoid tissue and an increase in tetracycline uptake. In the three patients with symptoms, bone pain subsided, fractures healed, and urinary loss of calcium and phosphate decreased. Thus, vitamin D may be a factor in the genesis of parenteral nutrition-induced metabolic bone disease.

Topics: 25-Hydroxyvitamin D 2; Adult; Bone and Bones; Bone Diseases, Metabolic; Calcium; Dihydroxycholecalciferols; Ergocalciferols; Female; Fluorides; Humans; Male; Middle Aged; Osteomalacia; Parenteral Nutrition; Parenteral Nutrition, Total; Phosphates

Topics: 25-Hydroxyvitamin D 2; Ergocalciferols; Female; Humans; Hydroxycholecalciferols; Infant; Infant, Newborn; Osteomalacia; Postoperative Complications; Rickets; Vitamin D

Vitamin D appears to influence parathyroid function indirectly through its effects on calcium metabolism rather than by a direct action of its metabolites on the parathyroid glands. In states of both secondary and primary hyperparathyroidism, the quantitative production of 1,25-(OH)2D may be determined by the prevailing concentration of serum 25-(OH)D but there appears to be some constraint that limits the formation of 1,25-0(OH)2D when the provision of its precursor exceeds the physiological. From the absence of this constraint in 'type 2 vitamin D dependency' it is inferred that it may operate through 'self-inhibition' of the renal production of 1,25-(OH)2D. It is shown that the level of serum 25-(OH)D may always exert some influence on the production of 1,25-(OH)2D and that this effect is facilitated by hyperparathyroidism. In developing vitamin D deficiency the reactive secondary hyperparathyroidism may thus function as an adaptive mechanism that sustains the level of serum 1,25-(OH)2D in the face of a diminishing serum 25-(OH)D. Failure of this adaptation and the development of a critical deficiency of 1,25-(OH)2D is regarded as the direct cause of defective mineralisation of bone. This concept would explain the absence of osteomalacia in some patients with very low levels of serum 25-(OH)D and the occurrence of defective osseous mineralisation in hypoparathyroidism.

Topics: 25-Hydroxyvitamin D 2; Calcitriol; Ergocalciferols; Humans; Hyperparathyroidism; Hyperparathyroidism, Secondary; Hypocalcemia; Osteomalacia; Parathyroid Hormone; Vitamin D; Vitamin D Deficiency

Hypercalcaemia developed in 21 patients due to vitamin-D poisoning; 2 were poisoned twice and 2 were poisoned three times. All patients had taken milligram doses of vitamin D, which for 5 patients was inappropriate. For the other 16 patients (mainly with hypoparathyroidism) milligram doses of vitamin D were appropriate; the patients were poisoned either early in therapy, trying to correct the plasma-calcium too quickly, or, later, because of failure to follow up patients properly. 2 patients died as a result of their intoxication. Constant vigilance is essential when patients are taking large doses of vitamin D.

Topics: Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Follow-Up Studies; Humans; Hypercalcemia; Hyperparathyroidism; Iatrogenic Disease; Osteomalacia; Osteoporosis; Patient Dropouts; Self Administration; Self Medication

Topics: Calcium; Ergocalciferols; Female; Humans; Hyperparathyroidism; Middle Aged; Osteomalacia; Parathyroid Hormone; Phosphates

The histological and biochemical response of osteomalacia has been studied in four patients with primary biliary cirrhosis, who were treated with oral 25-hydroxyvitamin D3, 50 microgram daily, or intramuscular vitamin D2, 150,000 units once weekly, for five to 12 months. All patients showed complete histological healing of osteomalacia, despite rapidly deteriorating liver function in three. Plasma 25-hydroxyvitamin D concentrations were low in all patients before treatment, but became normal during either vitamin therapy. Serum calcium and phosphate levels, and urinary calcium excretion were not always reliable in predicting the histological response to treatment. Serum alkaline phosphatase activity decreased in all patients during vitamin D therapy. We conclude that both high-dose parenteral vitamin D2 and oral 25-hydroxyvitamin D3 may be effective in healing osteomalacia associated with primary biliary cirrhosis. Measurement of plasma 25-hydroxyvitamin D levels during vitamin D therapy provides useful information about 25-hydroxylation of the parent vitamin and intestinal absorption of orally administered 25-hydroxyvitamin D3.

Topics: Administration, Oral; Aged; Ergocalciferols; Female; Humans; Hydroxycholecalciferols; Injections, Intramuscular; Liver Cirrhosis, Biliary; Male; Middle Aged; Osteomalacia

A 28-yr-old woman presented with hypocalcemia, hypophosphatemia, secondary hyperparthyroidism, and biopsy-proven osteomalacia despite treatment with vitamin D2, (17.5 mg/day). Three weeks after vitamin D2 treatment was stopped, she was found to have a low normal serum 25-hydroxyvitamin D (25OHD) and high serum 1 alpha, 25-dihydroxyvitamin D [1,25(OH)2D] of 18.6 ng/ml and 21.2 ng/dl, respectively. The fractional intestinal calcium absorption was low at 0.26. Treatment with 25OHD3 (20--50 micrograms/day) corrected the hypocalcemia and secondary hyperparathyroidism, raised intestinal calcium absorption, and reversed the skeletal lesions of osteomalacia. Serum 25OHD concentration rose to 51 ng/ml, while 1,25(OH)2D remained elevated. This case illustrates the probable operation of dual abnormalities in vitamin D metabolism. An impaired end organ responsiveness to 1,25(OH)2D was suggested by a low intestinal calcium absorption in the face of high serum 1,25(OH)2D. Moreover, there may have been a defective vitamin D-25-hydroxylase, since there was a relative refractoriness to treatment with large doses of vitamin D2, an inappropriately low serum 250HD after vitamin D2 therapy, and a responsiveness to treatment with 25OHD3.

Topics: Adult; Calcium; Ergocalciferols; Female; Humans; Hydroxycholecalciferols; Intestinal Absorption; Osteomalacia; Phosphates

Iliac crest biopsies and serum specimens were obtained from 36 non-dialyzed uraemic patients. The mean serum 25-hydroxycalciferol concentration of the patients was lower than that of normal subjects and a significant correlation was found between 25-hydroxycalciferol values and the severity of osteomalacia. Parathyroid osteopathy was significantly correlated with serum immunoreactive parathyroid hormone but not with serum 25-hydroxycalciferol values. While normal serum 25-hydroxycalciferol concentrations in uraemic patients do not exclude the presence of osteomalacia, a low concentration is virtually diagnostic of this disorder.

Topics: Antigens; Ergocalciferols; Humans; Kidney Failure, Chronic; Osteomalacia; Parathyroid Hormone

The biochemical changes observed in a patient with adult-onset hypophosphataemic osteomalacia after three weeks treatment with 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) followed by dihydrotachysterol (DHT) are reported. The treatment with 1,25-(OH)2D3 resulted in restoration of intestinal phosphate absorption to normal with a small rise in plasma phosphate concentration; there was no significant change in tubular reabsorption of phosphate. The tubular reabsorption of bicarbonate, which was initially low, returned almost into the normal range with normalisation of plasma bicarbonate concentration. Aminoaciduria decreased. There were no changes in plasma or urinary calcium but immunoreactive parathyroid hormone (i-PTH) which was initially elevated fell but still remained above the normal range. These changes were maintained after replacing the 1,25-(OH)2D3 treatment with dihydrotachysterol (DHT).

Topics: Amino Acids; Bicarbonates; Calcium; Chlorides; Dihydrotachysterol; Dihydroxycholecalciferols; Ergocalciferols; Female; Humans; Hydroxycholecalciferols; Intestinal Absorption; Middle Aged; Osteomalacia; Phosphates

Histological examination of bone from 25 patients with small-intestinal resection showed that 9 (36%) had osteomalacia, which was severe in 5 and mild in 4. The serum-alkaline-phosphatase concentration was raised in all patients with severe osteomalacia, but serum calcium, phosphate, and alkaline-phosphatase concentrations were normal in the 4 patients with mild disease, 2 of whom had symptoms. Osteomalacia was diagnosed radiologically in only 3 patients. Osteomalacia appears to be commoner in patients with small-intestinal resection than has previously been thought, and bone biopsy is essential if all cases are detected. Although high-dose parenteral vitamin-D therapy is usually effective in the treatment of osteomalacia after small-intestinal resection, our findings showed that oral vitamin-D metabolites and their analogues may also be effective. This has important practical advantages.

Topics: Administration, Oral; Adult; Aged; Alkaline Phosphatase; Bone and Bones; Calcium; Crohn Disease; Ergocalciferols; Female; Humans; Ileum; Injections, Intramuscular; Jejunum; Malabsorption Syndromes; Male; Middle Aged; Osteomalacia; Phosphates; Postoperative Complications; Vitamin D

Twenty of 32 patients with either chronic cholestatic or hepatocellular liver disease had bone pain or recent fractures. On bone biopsy five patients had normal bone, 15 had osteomalacia, five had osteoporosis, and seven had a combination of osteomalacia and osteoporosis. In the presence of osteoporosis, osteomalacia was minimal or absent. There was no biochemical, radiological, or histological evidence of excess parathyroid activity. No significant correlations were demonstrated between the plasma and urinary biochemical findings and the presence of either osteoporosis or osteomalacia and bone biopsy was essential for correct diagnosis. There was no statistical relationship between low serum 25-hydroxy vitamin D values and the presence of osteomalacia. Bone disease was not prevented by regular intramuscular vitamin D2, although biochemical changes were improved. Drugs such as corticosteroids and cholestyramine may be important aetiological factors in hepatic osteodystrophy.

Topics: Adult; Bone and Bones; Cholestasis; Chronic Disease; Ergocalciferols; Female; Humans; Hydroxycholecalciferols; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Osteomalacia; Osteoporosis; Parathyroid Glands

Topics: Animals; Bone and Bones; Calcium; Disease Models, Animal; Ergocalciferols; Osteomalacia; Phenytoin; Rats

The ability to 25-hydroxylate vitamin D was investigated in thirty-nine patients with symptomatic primary biliary cirrhosis (P.B.C.). In seven previously untreated patients serum-25-hydroxy-vitamin-D (25-OHD) concentration increased after regular monthly injections of vitamin D. After a single injection of vitamin D in eight P.B.C. patients serum-25-OHD did not change significantly over 12 days; in contrast there were significant increases in eight normal subjects and in seven patients with nutritional osteomalacia. Twenty-three of twenty-five P.B.C. patients on regular vitamin-D therapy had normal serum-25-OHD values. These results indicate that serum-25-OHD concentrations become normal in P.B.C. if adequate amounts of vitamin D are presented to the liver as substrate.

Topics: Adult; Aged; Ergocalciferols; Female; Follow-Up Studies; Humans; Hydroxycholecalciferols; Injections, Intramuscular; Liver; Liver Cirrhosis, Biliary; Male; Middle Aged; Osteomalacia; Vitamin D Deficiency

The intestinal absorption of 47Ca was studied in elderly patients. A standard dose of 10 muCi of 47Ca was given orally. The radioactivity was measured in the plasma, and expressed as percentage of the administered dose per litre plasma. As a control group served 12 patients aged 60-80 years, hospitalized for observation for various reasons, receiving no medical treatment and not suffering from any known metabolic bone diseases or other metabolic pathological conditions. Results of kinetic curves demonstrate in elderly patients a decreased absorption with maximum specific activity in plasma reached at 120 min, when compared to data from the literature referring to a group of young people with a mean age of 35 years. Oestrogen treatment, given as ethinyl oestradiol 10 mug once daily per os for 10 days proved to increase 47Ca absorption as was demonstrated in 2 patients with osteoporosis. The effect of calcitonin (160 MRC units given 45 min before the test) on calcium absorption, in 5 patients with Paget's disease or osteoporosis appears as biphasic: in the first hour depressing calcium absorption and then in the second and third hours increasing the absorption, suggesting a hyperparathyroid state secondary to the calcitonin effect. The vitamin D2 treatment proved to increase calcium absorption.

Topics: Aged; Calcitonin; Calcium Radioisotopes; Ergocalciferols; Estradiol; Female; Humans; Intestinal Absorption; Male; Middle Aged; Osteitis Deformans; Osteomalacia; Osteoporosis

Quantitative morphometric analyses of iliac crest biopsies from 20 epileptic patients receiving chronic anticonvulsant therapy have been performed before and after 4-8 months of vitamin D2 treatment with 9 000 U per day. Biochemical quantities, including serum 25-hydroxycholecalciferol (25-HCC) and serum parathyroid hormone (iPTH), were measured. The anticonvulsant osteomalacia found in the initial bone biopsies was characterized by an increased amount of ummineralized bone, an increased bone resorption and, contrary to vitamin D deficiency, an increased bone mineralization and bone formation. Bone resorption and bone formation were probably equally increased since the amount of cancellous bone was normal. Except for a slight increase in osteoidcovered surfaces and osteoclastic resorption surfaces, the bone changes were normalized after vitamin D2 treatment, leading to a mean serum level of 25-HCC 2.4 times above normal. Serum iPTH was normal before and unchanged during D2 therapy. The urinary calcium excretion remained decreased. The investigation characterizes anticonvulsant osteomalacia as a specific bone disease different from that of vitamin D deects of vitamin D metabolites on receptor cells.

Topics: Adult; Anticonvulsants; Bone and Bones; Bone Resorption; Calcium; Epilepsy; Ergocalciferols; Female; Humans; Hydroxycholecalciferols; Male; Middle Aged; Osteomalacia; Parathyroid Hormone; Phosphorus; Time Factors

Topics: Bone and Bones; Epilepsy; Ergocalciferols; Humans; Hydroxycholecalciferols; Ileum; Osteomalacia; Parathyroid Hormone; Phenytoin

A survey has been carried out on 206 healthy Pakistani women attending with their sick children at the paediatric outpatients department and 252 pregnant Pakistani women near term attending the antenatal clinic of the Karachi Prosgraduate Medical Centre. 12-6% of helathy women and 33% of pregnant women had biochemical abnormalities in serum calcium, phosphorus, and alkaline phosphatase which were corrected with subsequent administration of vitamin D. The absence of clinical disease has been ascribed to the supplementation received through the ultraviolet irradiation of the skin.

Topics: Alkaline Phosphatase; Calcium; Ergocalciferols; Female; Humans; Osteomalacia; Pakistan; Phosphates; Pregnancy; Pregnancy Complications

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

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

Topics: Adult; Ergocalciferols; Humans; Hydroxycholecalciferols; Intestinal Absorption; Male; Middle Aged; Osteomalacia; Phosphates; Phosphorus Radioisotopes

Topics: Adult; Anticonvulsants; Epilepsy; Ergocalciferols; Female; Humans; Osteomalacia

Topics: Adolescent; Adult; Ergocalciferols; Female; Humans; Hyperparathyroidism, Secondary; Male; Osteomalacia; Vitamin D Deficiency

Topics: Adult; Animals; Ergocalciferols; Female; Humans; Osteomalacia; Rats; Vitamin D; Vitamin D Deficiency

A case of hypophosphataemic osteomalacia occurring in association with a carcinoma of prostate is described. Although only palliative treatment to the primary tumour was possible, worthwhile remission of bone symptoms, due to osteomalacia, was achieved with pharmacological doses of vitamin D. The presence of extensive skeletal metastases modified the radiological features of osteomalacia. Major alterations in the distribution of calcium within the skeleton were observed during a period when total body calcium remained unaltered. This observation may be of relevance to other cases in which osteosclerotic metastases develop.

Topics: Acid Phosphatase; Aged; Body Weight; Bone and Bones; Bone Neoplasms; Calcium; Carcinoma; Ergocalciferols; Humans; Male; Neoplasm Metastasis; Osteomalacia; Prostatic Neoplasms; Radiography; Vitamin D

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: Adolescent; Anticonvulsants; Body Height; Body Weight; Calcium; Child; Dihydrotachysterol; Epilepsy, Tonic-Clonic; Ergocalciferols; Humans; Hypocalcemia; Hypoparathyroidism; Male; Middle Aged; Osteomalacia; Rickets; Time Factors; Ultraviolet Therapy; 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

Calciferol therapy for 12 months in white, Asian, and West Indian schoolchildren resulted in a highly significant increase in height and weight when compared with schoolchildren not so treated. The rate of fall of serum alkaline phosphatase was similar in both the treated and untreated schoolchildren and in other children treated in hospital for rickets. Dietary studies on 9% of the total survey by weighed inventory methods showed a low average intake of vitamin D, while random estimates of 25-hydroxycalciferol levels on 6% of the children were less than 3.8 ng/ml in 40% of those studied (principally Asian). It was concluded that there was a significant problem of vitamin D deficiency among Asian and West Indian teenagers and that white children were also affected to a less degree.

Topics: Adolescent; Alkaline Phosphatase; Asia; Body Height; Body Weight; Calcium, Dietary; Diet; Diet, Vegetarian; Emigration and Immigration; England; Ergocalciferols; Female; Growth Disorders; Humans; Hydroxycholecalciferols; Male; Osteomalacia; Protein Binding; Rickets; Sunlight; Vitamin D Deficiency; West Indies

Topics: Adult; Aged; Alkaline Phosphatase; Analgesics; Bicarbonates; Bone Diseases; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Osteitis Fibrosa Cystica; Osteomalacia; Parathyroid Hormone; Substance-Related Disorders

Topics: Anticonvulsants; Asia; Bone Resorption; Calcium; Calcium, Dietary; Epilepsy; Ergocalciferols; Humans; Hydroxycholecalciferols; Hyperparathyroidism; Hypoparathyroidism; Kidney; Kidney Failure, Chronic; Osteomalacia; Pigmentation; Renal Dialysis; Rickets; Scotland; Ultraviolet Rays; Vitamin D

Topics: Adult; Alkaline Phosphatase; Bone and Bones; Calcium; Epilepsy; Ergocalciferols; Female; Humans; Male; Middle Aged; Minerals; Osteomalacia; Phenytoin; Time Factors

Topics: Ergocalciferols; Humans; Hydroxycholecalciferols; Hydroxylation; Hyperparathyroidism; Methods; Osteomalacia; Osteoporosis; Radioimmunoassay; Seasons; Vitamin D

Topics: Adult; Anticonvulsants; Back Pain; Depression; Electroencephalography; Electromyography; Ergocalciferols; Female; Folic Acid; Hemoglobins; Humans; Intelligence; Microscopy, Electron; Muscular Diseases; Osteomalacia; Paralysis; Phenobarbital; Phenytoin; Thiazines; Vitamin D

Topics: Aged; Alkaline Phosphatase; Bone and Bones; Ergocalciferols; Female; Humans; Male; Osteomalacia; Osteoporosis; Radiography

Topics: Adult; Calcium, Dietary; Ergocalciferols; Female; Humans; Middle Aged; Osteomalacia

Topics: Acidosis, Renal Tubular; Adult; Bicarbonates; Ergocalciferols; Female; Humans; Kidney Diseases; Middle Aged; Osteomalacia; Sodium

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: Amino Acids; Calcium; Drug Resistance; Ergocalciferols; Ethylenediamines; Female; Glycine; Humans; Injections, Intravenous; Knee; Osteomalacia; Parathyroid Hormone; Pelvic Bones; Phosphorus; Radiography

Topics: Adolescent; Adult; Alkaline Phosphatase; Deficiency Diseases; Ergocalciferols; Female; Humans; India; Male; Metabolism, Inborn Errors; Middle Aged; Osteomalacia; Pakistan; Radiography; Urban Population; Vitamin D

Topics: Aged; Alkaline Phosphatase; Biopsy; Calcium; Ergocalciferols; Female; Humans; Ilium; Male; Osteomalacia; Phosphates; Radiography

Topics: Adolescent; Adult; Ergocalciferols; Glomerular Filtration Rate; Humans; Kidney; Osteomalacia; Phosphates; Phosphorus; Rickets

The investigation and treatment of osteomalacia are described in four patients with epilepsy treated with long-term anticonvulsant therapy. It is suggested that drug-mediated enzyme induction may be the mechanism responsible by causing a greatly increased inactivation of vitamin D in these patients.

Topics: Adolescent; Adult; Alkaline Phosphatase; Anticonvulsants; Biopsy; Calcium; Enzyme Induction; Epilepsy; Ergocalciferols; Female; Humans; Male; Middle Aged; Osteomalacia; Phenytoin; Phosphorus; Primidone; Vitamin D

A patient with Wilson's disease presented at the age of 41 with a neurological defect and gross osteomalacia secondary to a defect of renal tubular reabsorption. He also showed the unusual features of a renal stone in the presence of the Fanconi syndrome and a relatively low alkaline phosphatase level, possibly due to the additional inherited defect of hypophosphatasia. During four years of treatment with penicillamine and calciferol clinical improvement was spectacular. Details of amino-acid clearances before and after treatment are given, and the results suggest that, as in the brain and the liver, the function of the distal renal tubules may be restored in Wilson's disease when copper is removed.

Topics: Adult; Alkaline Phosphatase; Amino Acids; Ergocalciferols; Fanconi Syndrome; Hepatolenticular Degeneration; Humans; Hypophosphatasia; Kidney; Kidney Calculi; Male; Metabolic Clearance Rate; Neurologic Manifestations; Osteomalacia; Penicillamine; Sex Chromosome Aberrations

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

Topics: Adult; Calcium; Diet Fads; Diet Therapy; Diet, Vegetarian; Dihydrotachysterol; Ergocalciferols; Female; Humans; Middle Aged; Osteomalacia; Phosphates; Vitamin D; Vitamin D Deficiency

Topics: Aged; Ergocalciferols; Female; Humans; Hyperparathyroidism; Osteomalacia; Postgastrectomy Syndromes

Topics: Aluminum; Bone Diseases; Calcification, Physiologic; Calcium; Diet; Ergocalciferols; Humans; Hydrogen-Ion Concentration; Hyperparathyroidism; Osteomalacia; Phosphorus; Renal Dialysis; Thyroidectomy; Vitamin D

Topics: Adult; Ergocalciferols; Female; Humans; Osteomalacia; Vitamin D; Vitamin D Deficiency

Topics: Adolescent; Adult; Anemia, Macrocytic; Bicarbonates; Calcium; Ergocalciferols; Female; Folic Acid Deficiency; Humans; Hypocalcemia; Middle Aged; Neurologic Manifestations; Osteomalacia; Pain; Seizures; Tetany; Vitamin B 12 Deficiency; Vitamin D; Vitamin D Deficiency

Topics: Abortion, Spontaneous; Anemia, Hemolytic, Congenital; Animals; Ascorbic Acid; Ergocalciferols; Female; Humans; Hydrocephalus; Infant, Newborn; Infant, Newborn, Diseases; Jaundice, Neonatal; Maternal-Fetal Exchange; Osteomalacia; Pregnancy; Pregnancy, Prolonged; Pyridoxine; Rats; Scurvy; Seizures; Skull; Vitamin A; Vitamin B 12; Vitamin E; Vitamin K; Vitamins

Topics: Adolescent; Bone Neoplasms; Calcinosis; Calcium; Calcium Isotopes; Ergocalciferols; Feces; Geriatrics; Humans; Hyperparathyroidism; Hypoparathyroidism; Inositol; Intestinal Absorption; Malabsorption Syndromes; Neoplasm Metastasis; Neoplasms; Osteitis Deformans; Osteomalacia; Pancreatitis; Sarcoidosis; Tetany; Urine

Topics: Adult; Ergocalciferols; Humans; Kidney Diseases; Kidney Tubules; Osteomalacia; Phosphates; Vitamin D; Vitamins

Topics: Adolescent; Amino Acid Metabolism, Inborn Errors; Chronic Kidney Disease-Mineral and Bone Disorder; Dipeptides; Ergocalciferols; Glycine; Glycosuria; Glycosuria, Renal; Humans; Hydroxyproline; Kidney Function Tests; Osteomalacia; Osteoporosis; Phosphates; Phosphorus; Phosphorus Metabolism Disorders; Radiography; Renal Aminoacidurias; Renal Tubular Transport, Inborn Errors; Rickets; Rickets, Hypophosphatemic; Urine

Topics: Alkalies; Aluminum; Bicarbonates; Blood Chemical Analysis; Bone Diseases; Calcium; Ergocalciferols; Humans; Kidney Diseases; Kidney Failure, Chronic; Osteitis Fibrosa Cystica; Osteomalacia

Topics: Blood Protein Disorders; Calcium Metabolism Disorders; Ergocalciferols; Fractures, Spontaneous; Gastroenterology; Humans; Kidney Diseases; Kidney Glomerulus; Liver Cirrhosis; Osteomalacia; Osteoporosis; Phosphorus Metabolism Disorders; Rib Fractures; Vitamin D Deficiency

Topics: Androgens; Blood Chemical Analysis; Bone Diseases; Calcium Isotopes; Calcium Metabolism Disorders; Citrates; Ergocalciferols; Estrogens; Hypocalcemia; Osteomalacia; Osteopetrosis; Osteoporosis; Parathyroid Glands; Pharmacology; Phosphates; Physiology; Radiometry; Strontium Isotopes; Urine

Topics: Ascorbic Acid; Ergocalciferols; Humans; Osteomalacia; Vitamins

Topics: Cholestanes; Ergocalciferols; Humans; Medical Records; Osteomalacia; Vitamin D; Vitamins