25-hydroxyvitamin-d-2 and Osteomalacia

Paget's disease of bone (PDB) is the second most common metabolic bone disease. Bisphosphonates (BPs) are currently the drugs of choice for PDB. PDB and osteomalacia are both common in the elderly. The concept of relative vitamin D deficiency in patients with PDB was suggested long ago, but it has not yet elucidated. Both diseases predispose to fractures, but their combined action to fragility has not been studied yet. The older BPs, mainly etidronate, further inhibit bone mineralization. Mineralization defects have also been described in patients with PDB treated with pamidronate. Moreover, hypocalcemia and secondary hyperparathyroidism after treatment with BPs have been described in PDB. Hypocalcemia seems to be more severe after treatment with the more potent, intravenous zoledronic acid, which is currently the treatment of choice for PDB. The counteracting hyperparathyroidism pathophysiologically intends to increase renal reabsorption of calcium and 1.25-dihydroxy vitamin D production and to stimulate osteoclasts in order to prevent long-term hypocalcemia. However, the effect of PTH on osteoclasts is, at least partly, restricted in patients taking BPs. Secondary hyperparathyroidism is a potentially detrimental condition, especially in patients already suffering from another bone disease. Serum calcium and vitamin D deficiency should be restored before BP treatment and calcium and vitamin D administration should be possibly continued for longer after achieving normocalcemia, which may shorten the duration of secondary hyperparathyroidism. QUICK SUMMARY: Mineralization defects and hypocalcemia with secondary hyperparathyroidism have been described in patients with Paget's disease of bone treated with bisphosphonates. Secondary hyperparathyroidism may be a potentially detrimental condition for patients with Paget's disease of bone.

Topics: 25-Hydroxyvitamin D 2; Bone Density Conservation Agents; Calcifediol; Calcium Carbonate; Dietary Supplements; Diphosphonates; Drug Monitoring; Humans; Hyperparathyroidism, Secondary; Hypocalcemia; Osteitis Deformans; Osteomalacia; Vitamin D

Topics: 25-Hydroxyvitamin D 2; Adenocarcinoma; Aged; Aged, 80 and over; Alkaline Phosphatase; Biopsy; Bone Neoplasms; Calcitriol; Humans; Ilium; Male; Osteomalacia; Phosphates; Prostatic 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

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

The objective of the study was to evaluate bone mass status (as measured by bone ultrasound) in patients on anticonvulsant therapy, and the influence that Vitamin D administration exerts over it.. We measured and compared the basal serum levels of 25(OH)D3, parathyroid hormone (PTH), and phalangeal bone ultrasound (Ad-SOS), in 30 adult patients who were taking anticonvulsant drugs, with a control group of similar age and sex. We then gave the patients a large oral dose of 3 mg (120.000 UI) of 25(OH)D3, and repeated the measurements after one month.. Basal 25(OH)D3 and Ad-SOS values were significantly lower, and PTH values significantly higher (P< 0.0001 in all), in the patient group. The low Ad-SOS values for the patients were independent of the treatment, but directly related to basal 25(OH)D3 levels (r = 0.45, P<0.01). There was a negative association between PTH and 25(OH)D3 (r = -0.64, P<0.0001), and no correlation between PTH y Ad-SOS (r = -0.20, p NS). After ingestion of the large dose of the vitamin D, the patient group registered a significant (P<0.0001) increase in 25(OH)D3 levels, their Ad-SOS values increased (P<0.0001) nearly to the mean basal value of the control group, and PTH decreased significantly (P<0.0001).. These findings justify the need to assure adequate vitamin D intake in patients being treated with anticonvulsants, independently of the treatment, age, sex, and activity status, in order to prevent osteomalacia.

Topics: 25-Hydroxyvitamin D 2; Adult; Aged; Anticonvulsants; Bone and Bones; Calcifediol; Carbamazepine; Epilepsy; Female; Fingers; Humans; Male; Middle Aged; Osteomalacia; Parathyroid Hormone; Phenytoin; Ultrasonography; Valproic Acid; Vitamin D

Serum vitamin D (25-hydroxyvitamin D (25OHD)) may influence serum parathyroid hormone (PTH) levels and bone mineral density (BMD). In the present study, we assessed serum 25OHD concentration and its association with PTH and BMD in urban males from Guiyang (N26.57°), the capital city of Guizhou province, Southwest China. We recruited 634 males aged >20 years from the Guiyang Health Measures Survey, and stratified them into three groups according to age: young (20-39 years), middle aged (40-59 years) and older (60-79 years). We measured serum concentrations of 25OHD, PTH levels and BMD of the lumbar spine (L1-L4), femoral neck and total hip. In addition, we also explored the relationship between 25OHD and lifestyle, socio-economic characteristics and medical history by applying covariance analysis and locally weighted regression plots. The results showed that serum 25OHD was 75 nmol/l in 12·6 % of the subjects. Higher level of serum PTH was detected in relation to lower concentrations of serum 25OHD up to 50 nmol/l. A negative correlation between serum 25OHD and PTH concentrations was observed (r -0·207, P=0·003). Mean concentration of serum PTH increased gradually and plateaued while concentrations of serum 25OHD decreased to 50 nmol/l. Gradual increase in serum PTH was observed as 25OHD concentration was <25 nmol/l (P=0·004). BMD values at all sites were greater in the higher serum 25OHD concentration group. This study shows that low concentrations of serum 25OHD were common in males, and bone health was likely to be improved when serum 25OHD values were between 30 and 50 nmol/l.

Topics: 25-Hydroxyvitamin D 2; Adult; Aged; Aging; Bone Density; Calcifediol; China; Cohort Studies; Cross-Sectional Studies; Humans; Hyperparathyroidism, Secondary; Male; Middle Aged; Nutrition Surveys; Osteomalacia; Parathyroid Hormone; Risk; Seasons; Urban Health; Vitamin D Deficiency; Young Adult

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

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

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

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

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

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

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

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