Unusual cases of chronic intoxication by vitamin D

A 62-year-old man was hospitalized for recent renal colic and neurologic disorders. Routine biochemistry indicated the presence of hypercalcemia (serum total calcium = 15.3 mg/100 mL) and renal failure (serum creatinine = 3.72 mg/100 mL). The patient reported that he had been on treatment with a slow-release multivitamin preparation containing vitamin D and vitamin A, administered by i.m. injection. Plasma 25-OH vitamin D was > 150 ng/mL (normal range 16-74 ng/mL), plasma 1,25-(OH)2 vitamin D was 32.5 pg/mL (normal range 14-60 pg/mL), plasma parathyroid hormone 1.3 pg/mL (normal range 10-65 pg/mL). There were calcifications of left and right iliac artery at abdomen x-ray. Ultrasound and computed tomography of the glutei showed alterations of skeletal muscle and calcifications. Immediate treatment with infusion of isotonic saline, furosemide and prednisone induced rapid control of hypercalcemia and renal failure. Chronic treatment per os was discontinued after six months. The patient reported that the treatment with vitamin D had been prescribed by a physician also to his wife (55-year-old). For the woman, routine biochemistry indicated the presence of hypercalcemia (serum total calcium = 11.3 mg/100 mL) and renal failure (serum creatinine = 1.8 mg/ mL). Plasma 25-OH vitamin D was > 150 ng/mL, plasma 1,25-(OH)2 vitamin D 47.9 pg/mL, plasma parathyroid hormone was 2.5 pg/mL. Hypercalcemia was acutely treated by oral hydration, furosemide, and prednisone. Chronic treatment per os was discontinued after five months.     

Postoperative tetany in Graves disease: important role of vitamin D metabolites

OBJECTIVE: To test the authors' hypothesis of the causal mechanism(s) of postoperative tetany in patients with Graves disease. SUMMARY BACKGROUND DATA: Previous studies by the authors suggested that postoperative tetany in patients with Graves disease occurs during the period of bone restoration and resulted from continuation of a calcium flux into bone concomitant with transient hypoparathyroidism induced by surgery. PATIENTS AND METHODS: A prospective study was carried out to investigate sequential changes in serum levels of intact parathyroid hormone (iPTH), calcium and other electrolytes, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH)2D), and bone metabolic markers in 109 consecutive patients with Graves disease who underwent subtotal thyroidectomy. RESULTS: Preoperative serum iPTH levels negatively correlated with ionized calcium levels and positively correlated with 1,25(OH)2D or 1,25(OH)2D/25OHD. After the operation, there was a significant decline in levels of ionized calcium, magnesium, and iPTH. Serum iPTH was not detected in 15 patients after surgery. Four of these 15 patients, and 1 patient whose iPTH level was below normal, developed tetany. Preoperative serum ionized calcium levels were significantly lower, and iPTH levels were higher, in the 5 patients with tetany than in the 11 patients who did not develop tetany despite undetectable iPTH levels. The tetany group had significantly lower serum 25OHD levels and higher 1,25(OH)2D levels, and had increased 1,25(OH)2D/25OHD as an index of the renal 25OHD-1-hydroxylase activity than those in the nontetany group. These results suggest that patients with a high serum level of iPTH as a result of low serum calcium levels (secondary hyperparathyroidism) are susceptible to tetany under conditions of hypoparathyroid function after surgery. CONCLUSIONS: Postoperative tetany occurs in patients with secondary hyperparathyroidism caused by a relative deficiency in calcium and vitamin D because of their increased demand for bone restoration after preoperative medical therapy concomitant with transient hypoparathyroidism after surgery. Calcium and vitamin D supplements may be recommended before and/or after surgery for patients in whom postoperative tetany is expected to develop.     

A trial of suppressing secondary hyperparathyroidism by oral high dose therapy of 1, 25-dihydroxyvitamin D3

We reported a successful treatment of secondary hyperparathyroidism by intermittent oral administration of high dose of 1, 25 dihydroxycholecalciferol [1.25-(OH)2D3] in three patients on maintenance hemodialysis. Dialysis durations were 4 months in case 1, 6.5 years in case 2 and 12.5 years in case 3. The levels of c-PTH ranged from 4.7 ng/ml to 94.2 ng/ml. 1, 25-(OH)2D3 in dosages up to 8.0 micrograms was given once a week just after hemodialysis. Before the administration and after 48 hours, serum Ca, serum Pi, serum Mg, c-PTH and highly sensitive PTH were assayed. There was a significant correlation between max. plasma concentration of 1, 25-(OH)2D and logarithm of the dose in all patients. The max. plasma level of 1, 25-(OH)2D reached 25-(OH)2D reached to 200 pg/ml at 4 hours after the oral administration of 8.0 micrograms. Their thresholds of 1, 25-(OH)2D level which could decrease the PTH levels were elevated proportionally to their dialysis durations. Case 1 required 4.0 micrograms to suppress secondary hyperparathyroidism, whereas, case 2 and 3 did 8.0 micrograms of 1, 25-(OH)2D3. Severe hypercalcemia was not observed during a high dose treatment. In conclusion, we have succeeded in treating refractory secondary hyperparathyroidism by intermittent oral administration of high dose 1, 25-(OH)3D3. This therapy is recommended to start in the earlier stage of a long-term dialysis in order to prevent severe secondary hyperparathyroidism and bone disease.     

New vitamin D analogs

BACKGROUND: 1,25-(OH)2D3 (calcitriol) controls parathyroid gland growth and suppresses the synthesis and secretion of parathyroid hormone. Because of this, 1,25-(OH)2D3 has been used successfully for the treatment of secondary hyperparathyroidism, which almost always accompanies renal failure. However, the potent effect of 1,25-(OH)2D3 on intestinal calcium and phosphorus absorption and bone mineral mobilization often leads to the development of hypercalcemia and hyperphosphatemia precluding 1,25-(OH)2D3 therapy. METHODS: This has led to the development of vitamin D analogs that retain the suppressive action on PTH and parathyroid gland growth, but that have less calcemic and phosphatemic activity. Currently, two analogs, 19-nor-1,25-(OH)2D2 and 1,alpha(OH)D2, are being used for the treatment of secondary hyperparathyroidism in the United States, and two are being used in Japan, 22-oxa-calcitriol and 1,25-(OH)2-26,27F6 D3. RESULTS: All four analogs suppressed PTH, but had less calcemic and phosphatemic activity than 1,25-(OH)2D3. In rats, 19-nor-1,25-(OH)2D2 has been shown to be less calcemic and phosphatemic compared to 1,alpha(OH)D2. CONCLUSION: Therapeutic doses of 19-nor-1,25-(OH)2D2 could produce a lower Ca x P product compared to 1,alpha(OH)D2, which could be an important consideration in patient treatment. Further studies are necessary to define these differences and to understand the mechanisms behind the differential actions of vitamin D analogs.     

Severe vitamin D deficiency in chronic renal failure patients on peritoneal dialysis

The aim of this study was to evaluate the prevalence of vitamin D deficiency in chronic renal failure (CRF) patients on peritoneal dialysis (PD) and to correlate the findings with various demographic and renal osteodystrophy markers. METHOD: This cross-sectional, multicenter study was carried out in 273 PD patients with a mean age of 61.7 +/- 10.9 years and mean duration of PD 3.3 +/- 2.2 years. It included 123 female and 150 male patients from 20 centers in Greece and Turkey, countries that are on the same latitude, namely, 36-42 degrees north. We measured 25(OH)D3 and 1.25(OH)2D3 levels and some other clinical and laboratory indices of bone mineral metabolism. RESULTS: Of these 273 patients 92% (251 patients) had vitamin D deficiency i.e. serum 25(OH)D3 levels less than 15 ng/ml, 119 (43.6%) had severe vitamin D deficiency i.e., serum 25(OH)D3 levels, less than 5 ng/ml, 132 (48.4%) had moderate vitamin D deficiency i.e., serum 25(OH)D3 levels, 5-15 ng/ml, 12 (4.4%) vitamin D insufficiency i.e., serum 25(OH)D3 levels 15 - 30 ng/ml and only 10 (3.6%) had adequate vitamin D stores. We found no correlation between 25(OH)D3 levels and PTH, serum albumin, bone alkaline phosphatase, P, and Ca x P. In multiple regression analyses, the independent predictors of 25(OH)D3 were age, presence of diabetes (DM-CRF), levels of serum calcium and serum 1.25(OH)2D3. CONCLUSION: We found a high prevalence (92%) of vitamin D deficiency in these 273 PD patients, nearly one half of whom had severe vitamin D deficiency. Vitamin D deficiency is more common in DM-CRF patients than in non-DM-CRF patients. Our findings suggest that these patients should be considered for vitamin D supplementation.     

Relationship between serum 25-hydroxyvitamin D and bone resorption markers in vitamin D insufficiency

It is known that nursing-home patients with vitamin D insufficiency have elevated serum parathyroid hormone (PTH) as well as raised serum alkaline phosphatase (ALP). Although it is well known that vitamin D insufficiency and secondary hyperparathyroidism are common among the elderly in western countries, there is continuing controversy over the level of serum 25-hydroxyvitamin D [25(OH)D] necessary for bone health. We approached this issue by examining the relationships between serum 25(OH)D, ionized calcium, PTH, and ALP and the urinary bone resorption markers hydroxyproline, pyridinoline, and deoxypyridinoline, corrected for creatinine (OHPr/Cr, Pyd/Cr, and Dpd/Cr, respectively), in 486 postmenopausal women of mean age 63 (SD 9.5) years, who were referred to our osteoporosis and menopause clinics for investigation. When the patients were divided into two groups with 25(OH)D above and below 20 nmol/L, 30 nmol/L, 40 nmol/L, 50 nmol/L, 60 nmol/L, or 70 nmol/L, the most significant differences between the two groups thus derived was found at a serum 25(OH)D level of 60 nmol/L (P < 0.001 for all markers). The most significant difference between groups for serum PTH was found when the patients were divided at a serum 25(OH)D of 50 nmol/L. PTH, OHPr/Cr, Pyd/Cr, and ALP were inversely related to serum 25(OH)D. PTH was inversely related to serum ionized calcium. There was a trend for ionized calcium to be positively related to 25(OH)D, but this did not reach statistical significance. We conclude that rises in three bone resorption markers and ALP can be detected in postmenopausal women when the serum 25(OH)D level falls below 60 nmol/L. Levels above this may be required for optimal bone health.     

Effect of 2-methylene-19-nor-(20S)-1 alpha-hydroxy-bishomopregnacalciferol (2MbisP), an analog of vitamin D, on secondary hyperparathyroidism.

Vitamin D analogs are being developed that retain therapeutic effects but are less calcemic and phosphatemic, a concern in CKD patients who are prone to vascular calcification. We tested a new analog of vitamin D, 2MbisP, and found that it suppresses PTH at doses that do not affect serum Ca or P. INTRODUCTION: Calcitriol is used for the treatment of secondary hyperparathyroidism. However, its use is often limited by the development of hypercalcemia and hyperphosphatemia, an important consideration in patients with chronic kidney disease (CKD) because they are prone to vascular calcification. To minimize this toxicity, structural modifications in the vitamin D molecule have led to the development of calcitriol analogs with selective actions. MATERIALS AND METHODS: In this study, we compared the effects of 1,25(OH)(2)D(3) and a new analog, 2-methylene-19-nor-(20S)-1 alpha-hydroxy-bishomopregnacalciferol (2MbisP), on the development of secondary hyperparathyroidism and established secondary hyperparathyroidism in uremic rats and on mobilization of calcium and phosphorus from bone in parathyroidectomized rats. The clearance from circulation, half-life, and binding affinities to the vitamin D-binding protein and vitamin D receptor of this compound were also evaluated. RESULTS: Uremia produced a marked rise in plasma PTH, but treatment every other day for 2 wk with either 1,25(OH)(2)D(3) (4 ng) or 2MbisP (250, 750, 1500, or 3000 ng) suppressed this increase by >50%. The suppression by 1,25(OH)(2)D(3), however, was accompanied by increases in ionized calcium, phosphorus, and the calcium x phosphorus product, whereas these three parameters were unchanged by 2MbisP. The binding affinity of 2MbisP was 10-20 times less for the vitamin D receptor and 1000 times less for the serum vitamin D-binding protein compared with 1,25(OH)(2)D(3). Also, 2MbisP was cleared more rapidly from the circulation (t1/2 = 10 min) than 1,25-(OH)(2)D(3) (t1/2=7-9 h). In parathyroidectomized rats fed calcium-or phosphorus-deficient diets, daily injections of 2MbisP (1500 or 3000 ng), unlike 1,25(OH)(2)D(3) (50 ng), had no effect on calcium or phosphorus mobilization from bone. CONCLUSIONS: In uremic rats, 2MbisP can suppress PTH at doses that do not affect plasma calcium, phosphorus, and calcium x phosphorus product. This new vitamin D analog may represent an important tool in the treatment of secondary hyperparathyroidism in patients with CKD.     

Correction of preoperative vitamin D deficiency after Roux-en-Y gastric bypass surgery

BackgroundTo evaluate the adequacy of supplementation to correct preoperative vitamin D deficiency in adult patients during the year after Roux-en-Y gastric bypass (RYGB) surgery.MethodsThe medical records were reviewed and the preoperative and 12-month postoperative serum 25-hydroxyvitamin D [25(OH)D] levels were compared in patients who underwent RYGB from 2002 to 2004. The serum 25(OH)D levels were defined as being optimal (≥80 nmol/L), suboptimal (50–79 nmol/L), or deficient (<50 nmol/L). Patients with deficient 25(OH)D levels were prescribed 50,000 IU ergocalciferol weekly. The remaining patients averaged 710 IU supplemental vitamin D intake daily.ResultsThe mean patient age was 43.8 ± 10.7 years, and the mean preoperative body mass index was 51.8 ± 9.8 kg/m². Of the 95 patients with baseline and 12-month 25(OH)D levels, 89% were women. The mean preoperative 25(OH)D level was 49.7 ± 26.5 nmol/L; 34% had suboptimal 25(OH)D levels and 54% had deficient levels before surgery. Twelve months after surgery, those receiving 50,000 IU weekly (n = 40) had a mean 25(OH)D level of 69.2 ± 22.2 nmol/L; 63% had suboptimal and 8% deficient levels. Those taking 710 IU daily (n = 55) had a mean 25(OH)D level of 85.5 ± 33.0 nmol/L; 44% had suboptimal and 6% deficient levels.ConclusionVitamin D deficiency is prevalent in RYGB patients before surgery. The vitamin D status improved markedly after RYGB surgery with either 710 IU vitamin D daily or 50,000 IU weekly. Current supplementation practices do not appear to optimize the serum 25(OH)D levels and need to be more closely examined.     

High-dose oral vitamin D3 supplementation in rheumatology patients with severe vitamin D3 deficiency

ObjectivesRecent large trials indicate that adherence associated with a daily regimen of vitamin D is low and limits anti-fracture efficacy with vitamin D supplementation. The aim of this report is to describe changes of 25-hydroxyvitamin D (25(OH)D) serum concentrations achieved with a single oral dose of 300 000 IU vitamin D3.MethodsOver a course of 4 months, we identified 33 elderly with severe vitamin D deficiency (25(OH)D < 25 nmol/l) on admission to acute care. Patients were admitted for musculoskeletal pain, bone disease, or gait abnormalities. The mean age was 80.5 years (SD ± 6.1). All patients were treated with a single oral dose of 300 000 IU D3 in combination with 500–1000 mg calcium supplements per day depending on their dietary calcium intake.ResultsBaseline mean 25(OH)D serum concentrations were 15 nmol/l (SD ± 5.5). Mean 25(OH)D serum concentrations increased to 81.4 nmol/l (SD ± 29.7) at 3 months (29 patients) and were still 69.0 nmol/l (SD ± 17.9) at 6 months (26 patients). Mean serum calcium levels were 2.24 mmol/l (SD ± 0.11) at baseline, 2.28 mmol/l (SD ± 0.18) at 3 months, and 2.28 mmol/l (SD ± 0.13) at 6 months. Two patients with mild hypercalcemia (2.69 mmol/l) at 3 months had normal values at 6 months.ConclusionBased on our observations, a single oral dose of 300 000 IU vitamin D3 raises mean 25(OH)D serum concentrations to the target mean of above 75 nmol/l at 3 months and a mean level of 69 nmol/l at 6 months. As calcium absorption is enhanced with higher 25(OH)D serum concentrations, calcium supplementation may need downward adjustment with this regimen to avoid mild hypercalcemia.     

Taking vitamin D with the largest meal improves absorption and results in higher serum levels of 25‐hydroxyvitamin D

Many patients treated for vitamin D deficiency fail to achieve an adequate serum level of 25‐hydroxyvitamin D [25(OH)D] despite high doses of ergo‐ or cholecalciferol. The objective of this study was to determine whether administration of vitamin D supplement with the largest meal of the day would improve absorption and increase serum levels of 25(OH)D. This was a prospective cohort study in an ambulatory tertiary‐care referral center. Patients seen at the Cleveland Clinic Foundation Bone Clinic for the treatment of vitamin D deficiency who were not responding to treatment make up the stugy group. Subjects were instructed to take their usual vitamin D supplement with the largest meal of the day. The main outcome measure was the serum 259(OH)D level after 2 to 3 months. Seventeen patients were analyzed. The mean age (±SD) and sex (F/M) ratio were 64.5 ± 11.0 years and 13 females and 4 males, respectively. The dose of 25(OH)D ranged from 1000 to 50,000 IU daily. The mean baseline serum 25(OH)D level (±SD) was 30.5 ± 4.7 ng/mL (range 21.6 to 38.8 ng/mL). The mean serum 25(OH)D level after diet modification (±SD) was 47.2 ± 10.9 ng/mL (range 34.7 to 74.0 ng/mL, p < .01). Overall, the average serum 25(OH)D level increased by 56.7% ± 36.7%. A subgroup analysis based on the weekly dose of vitamin D was performed, and a similar trend was observed. Thus it is concluded that taking vitamin D with the largest meal improves absorption and results in about a 50% increase in serum levels of 25(OH)D levels achieved. Similar increases were observed in a wide range of vitamin D doses taken for a variety of medical conditions. © 2010 American Society for Bone and Mineral Research     

Longitudinal study of vitamin D metabolites after long bone fracture

Animal models suggest a key role for dihydroxylated vitamin D metabolites in fracture healing, as evidenced by increases in serum concentration of 24R,25‐dihydroxyvitamin D (24R,25[OH]₂D) after long bone fracture. Human studies investigating the kinetics of serum concentrations of 24R,25[OH]₂D, 1,25‐dihydroxyvitamin D (1,25[OH]₂D) and their parent metabolite 25‐hydroxyvitamin D (25[OH]D) are lacking. We, therefore, conducted a longitudinal study to determine whether total, free, or bioavailable concentrations of these vitamin D metabolites fluctuate in humans after long bone fracture. Twenty‐eight patients with cross‐shaft (diaphyseal) long bone fracture presenting to an emergency department in London, UK, were studied. Serum concentrations of 25(OH)D, 24R,25(OH)₂D, 1,25(OH)₂D, vitamin D binding protein, albumin, and calcium were determined within 48 hours of fracture and again at 1 and 6 weeks postfracture. Concentrations of free and bioavailable vitamin D metabolites were calculated using standard equations. No changes in mean serum concentrations of 25(OH)D or 24R,25(OH)₂D were seen at either follow‐up time point versus baseline. In contrast, mean serum 1,25(OH)₂D concentration declined by 21% over the course of the study, from 68.5 pmol/L at baseline to 54.1 pmol/L at 6 weeks (p < 0.05). This decline was associated with an increase in mean serum corrected calcium concentration, from 2.32 mmol/L at baseline to 2.40 mmol/L at 1 week (p < 0.001) that was maintained at 6 weeks. No changes in free or bioavailable concentrations of any vitamin D metabolite investigated were seen over the course of the study. We conclude that serum 1,25(OH)₂D concentration declines after long bone fracture in humans but that the serum 24R,25(OH)₂D concentration does not fluctuate. The latter finding contrasts with those of animal models reporting increases in serum 24R,25(OH)₂D concentration after long bone fracture.     

Evidence for abnormal regulation of circulating 1 alpha, 25-dihydroxyvitamin D in patients with pulmonary tuberculosis and normal calcium metabolism

Available evidence indicates that hypercalcemia in pulmonary tuberculosis results from increases in circulating 1 alpha, 25-dihydroxyvitamin D [1 alpha, 25(OH)2D]. To further characterize vitamin D metabolism in this disorder, the effects of vitamin D, 100,000 units a day for 4 days, were compared in 25 normal subjects and 11 patients with active pulmonary tuberculosis who were normocalcemic and had not had hypercalcemia. Serum calcium, phosphorus, 25-hydroxyvitamin D (25-OHD) and 1 alpha, 25(OH)2D were measured. Whereas vitamin D increased mean serum 25-OHD from 20 +/- 2 (+/- SE) to 40 +/- 5 ng/ml (P less than 0.001) and did not change mean serum 1 alpha, 25(OH)2D in the normals (33 +/- 2 vs. 31 +/- 2 pg/ml), it increased mean serum 25-OHD from 21 +/- 4 to 55 +/- 13 ng/ml (P less than 0.05) and mean serum 1 alpha, 25(OH)2D from 28 +/- 2 to 35 +/- 3 pg/ml (P less than 0.05) in the patients. Serum calcium was normal and remained within the normal range in all subjects and patients. The findings indicate that there is a modest but significant abnormality in the regulation of circulating 1 alpha, 25(OH)2D in normocalcemic patients with pulmonary tuberculosis. The results are similar to those previously reported by us in normocalcemic patients with sarcoidosis.     

Correction of preoperative vitamin D deficiency after Roux-en-Y gastric bypass surgery

BACKGROUND: To evaluate the adequacy of supplementation to correct preoperative vitamin D deficiency in adult patients during the year after Roux-en-Y gastric bypass (RYGB) surgery. METHODS: The medical records were reviewed and the preoperative and 12-month postoperative serum 25-hydroxyvitamin D [25(OH)D] levels were compared in patients who underwent RYGB from 2002 to 2004. The serum 25(OH)D levels were defined as being optimal (> or = 80 nmol/L), suboptimal (50-79 nmol/L), or deficient (<50 nmol/L). Patients with deficient 25(OH)D levels were prescribed 50,000 IU ergocalciferol weekly. The remaining patients averaged 710 IU supplemental vitamin D intake daily. RESULTS: The mean patient age was 43.8 +/- 10.7 years, and the mean preoperative body mass index was 51.8 +/- 9.8 kg/m2. Of the 95 patients with baseline and 12-month 25(OH)D levels, 89% were women. The mean preoperative 25(OH)D level was 49.7 +/- 26.5 nmol/L; 34% had suboptimal 25(OH)D levels and 54% had deficient levels before surgery. Twelve months after surgery, those receiving 50,000 IU weekly (n = 40) had a mean 25(OH)D level of 69.2 +/- 22.2 nmol/L; 63% had suboptimal and 8% deficient levels. Those taking 710 IU daily (n = 55) had a mean 25(OH)D level of 85.5 +/- 33.0 nmol/L; 44% had suboptimal and 6% deficient levels. CONCLUSION: Vitamin D deficiency is prevalent in RYGB patients before surgery. The vitamin D status improved markedly after RYGB surgery with either 710 IU vitamin D daily or 50,000 IU weekly. Current supplementation practices do not appear to optimize the serum 25(OH)D levels and need to be more closely examined.     

Hip fracture patients in India have vitamin D deficiency and secondary hyperparathyroidism

Summary

This study evaluated the parameters of bone mineral homeostasis including 25(OH)D and PTH in 90 Indian patients with hip fracture and 90 controls. Hypovitaminosis D, secondary hyperparathyroidism, and biochemical osteomalacia was present in 77, 69, and 50 % patients, respectively, significantly higher compared to controls. Vitamin D deficiency is an important risk factor for hip fracture.

Introduction

The prevalence of vitamin D deficiency is not well known in hip fracture patients from India. Therefore, the present study was conducted to evaluate the parameters of bone mineral homeostasis including 25(OH)D and intact PTH in hip fracture from North India.

Methods

Ninety consecutive patients with hip fracture and similar number of age- and sex-matched controls were enrolled in the study. The fasting venous samples were analyzed for 25-hydroxyvitamin D (25-OHD), intact parathyroid hormone (PTH), alkaline phosphatase (ALP), calcium, and phosphorus. Vitamin D deficiency was defined as serum 25-OHD of <20 ng/dl.

Results

The mean age of hip fracture subjects was 65.9?±?12.6 which was comparable in men and women. Majority of study subjects were women (70 women and 20 men). The serum 25(OH)D and calcium levels were significantly lower, whereas the intact PTH and ALP levels were significantly higher in patients compared to controls. There was significant negative correlation between serum 25(OH)D and PTH. In the hip fracture group, 76.7 % of the subjects had vitamin D deficiency, and 68.9 % had secondary hyperparathyroidism. In the control group, vitamin D deficiency and elevated PTH levels were seen in 32.3 and 42.2 %, respectively.

Conclusion

About three fourths of hip fracture patients have vitamin D deficiency, and two thirds have secondary hyperparathyroidism. Therefore, the serum 25-OHD level may be a useful index for the assessment of risk of hip fracture in India.     

Differences in vitamin D status and calcium intake: Possible explanations for the regional variations in the prevalence of hypercalcemia in tuberculosis

The prevalence of hypercalcemia in patients with untreated tuberculosis (TB) varies widely between countries. Since the vitamin D status and calcium intake are important determinants of hypercalcemia in TB, these two factors were compared among four populations (U.K., Hong Kong, Malaysia, Thailand) with a low prevalence (<3%) and two populations (Sweden, Australia) with a high prevalence (>25%). In the three Asian countries, the circulating vitamin D levels are abundant, but the calcium intakes are low. Subjects from the U.K. have the lowest circulating vitamin D level of all, although their calcium intake is high. In Sweden and Australia, both the circulating vitamin D levels and calcium intakes are high. Since serum 1,25(OH)₂D concentration will only be raised if its substance for extrarenal conversion, 25(OH)D, is plentiful and the effect of a given serum 1,25 (OH)₂D concentration on serum calcium is determined by the calcium intake, it is postulated that the regional variation in the prevalence of hypercalcemia in TB may be due to differences in the circulating vitamin D levels and calcium intakes in these populations. Received: 18 March 1996 / Accepted: 17 June 1996     

Use of vitamin D analogs in chronic renal failure

Renal osteodystrophy is the term used to describe the spectrum of bone diseases associated with chronic renal failure. Deficiency of 1,25-dihydroxycholecalciferol (calcitriol) plays a major role in the development of renal osteodystrophy, in particular the evolution of secondary hyperparathyroidism. In recent decades, our understanding of the complex interactions between calcium, phosphorus, vitamin D, and parathyroid hormone (PTH) has increased, resulting in a rational approach to therapy in which vitamin D analogs have become an essential component. The initial vitamin D analogs that have been in widespread clinical use include calcitriol (1,25-[OH](2)D(3)) and alfacalcidol (1alpha-[OH]D(3)). These agents have been extensively studied to optimize their effects on secondary hyperparathyroidism. The occurrence of significant hypercalcemia and hyperphosphatemia limiting their use has led to the development of alternative vitamin D analogs that effectively reduce PTH secretion without causing these complications. Recently, 3 such analogs, 22-oxa-1,25-(OH)(2)D(3) (OCT), 1alpha-(OH)D(2) (doxercalciferol), and 19-nor-1,25-(OH)(2)D(2) (paricalcitol), have been released for clinical use. Only paricalcitol has been studied in comparative human clinical trials with calcitriol in dialysis patients. Preliminary findings suggest a clinical advantage over calcitriol, however, analysis of the larger comparative studies are forthcoming.     

Association of vitamin D and knee osteoarthritis in younger individuals

BACKGROUND The incidence of primary osteoarthritis knee is gradually increasing among young individuals. The increasing prevalence of obesity, sedentary lifestyle, sporting activity, and vitamin D deficiency(VDD) has been hypothesized for this shifting disease trend. This study was designed to look for the association of serum vitamin D among these young arthritic patients.AIM To look for the association of serum vitamin D in younger knee osteoarthritis(KOA) patients.METHODS In a 2-year observational study, 146 non-obese KOA patients of 35-60 years were evaluated clinically(Knee injury and Osteoarthritis Outcome Score, KOOS) and radiologically(Kellegren-Lawrence stage, KL). The serum 25(OH)D level of these patients and 146 normal healthy individuals of same age group were estimated.RESULTS Both the groups were comparable in terms of age and sex. The average serum 25(OH)D level in healthy individuals and KOA patients was 45.83 ng/m L and 34.58 ng/m L, respectively(P 0.001). Inadequate serum 25(OH)D level( 30 ng/m L) was found in 46.57% of KOA patients and 24% of normal healthy participants indicating a significant positive association(odds ratio 2.77, 95%CI: 1.67-4.54, P 0.001). The 25(OH)D level in KL grade I, II, III and IV was 43.40, 30.59, 31.56 and 33.93 ng/m L respectively(no difference, P = 0.47). Similarly, the KOOS score in sufficient, insufficient and deficient groups were 65.31, 60.36 and 65.31, respectively(no difference, P = 0.051).CONCLUSION The serum 25(OH)D level is significantly low in younger KOA patients. However, the clinical and radiological severities have no association with serum vitamin D level.     

Vitamin D insufficiency defined by serum 25-hydroxyvitamin D and parathyroid hormone before and after oral vitamin D3 load in Japanese subjects

Vitamin D insufficiency is a risk for both skeletal and nonskeletal health. However, some ambiguity remains about threshold serum 25(OH)D for vitamin D insufficiency. To determine the threshold serum 25(OH)D to maintain normal calcium availability without elevation in serum parathyroid hormone (PTH) among Japanese subjects with various calcium intakes, we conducted a multicenter prospective open-labeled study. We recruited 107 ambulatory subjects without disorders affecting vitamin D metabolism to whom oral vitamin D₃ 800?IU/day for 4?weeks or 1,200?IU/day for 8?weeks was given. Serum 25(OH)D, PTH, calcium, phosphate, and magnesium were measured before and after vitamin D₃ supplementation. Calcium intake was assessed by questionnaires. When all the data were combined, serum 25(OH)D was negatively correlated with PTH. The cubic spline curve between serum 25(OH)D and PTH indicated PTH reached its plateau between 35 and 40?pg/ml at 25(OH)D between 25 and 30?ng/ml. Vitamin D₃ supplementation increased serum 25(OH)D and decreased PTH. Change in PTH correlated positively with baseline serum 25(OH)D. From the regression analyses, baseline serum 25(OH)D above 28?ng/ml corresponded to the threshold level without reduction in PTH after vitamin D₃ supplementation. In multivariate regression analyses, age but not calcium intake was a significant determinant of PTH. We concluded that a serum 25(OH)D level of 28?ng/ml was identified as a threshold for vitamin D insufficiency necessary to stabilize PTH to optimal levels.     

Oral calcitriol and calcium: efficient therapy for uremic hyperparathyroidism

Therapy with orally administered calcitriol often does not adequately control the biochemical manifestations of secondary hyperparathyroidism in uremic patients. This may be due to inadequate serum concentrations of 1.25(OH)2 vitamin D and/or to insufficient dietary calcium supplementation. In the present study, therefore, we examined the effect on parathyroid function of calcitriol and calcium carbonate, administered orally, in doses sufficient to normalize the serum 1.25(OH)2 vitamin D and calcium concentrations. After nine months of combined therapy, marked suppression of immunoreactive PTH occurred in the absence of hypercalcemia. Furthermore, prolonged therapy resulted in additional suppression of the PTH concentrations comparable in magnitude to that reported following intravenous calcitriol therapy and was associated with a mild degree of hypercalcemia similar to that which occurs with intravenous therapy. Euparathyroidism was achieved in 25% of the patients by 15 months of treatment. In conclusion, secondary hyperparathyroidism can be effectively controlled with combined oral therapy without significant hypercalcemia in selected patients with end-stage renal failure. This salutary effect may result from direct actions of 1.25(OH)2D on the parathyroid gland and/or gastrointestinal tract, or from an overall action of combined treatment to restore calcium homeostasis.     

The role of vitamin D in improving physical performance in the elderly

There is an ongoing debate over the role of serum 25(OH) vitamin D [25(OH)D] levels in maintaining or improving physical performance and muscle strength. Much of the controversy is because of the variability between studies in participants' characteristics, baseline serum 25(OH)D levels, and baseline physical functioning. The aim of this ancillary study conducted within a randomized controlled clinical trial was to investigate whether supplementation with 400 or 2000 IU vitamin D₃ daily for 6 months would improve measures of physical performance and muscle strength in a community‐dwelling elderly population aged 65 to 95 years. Those with the slowest gait speed improved their ability to do chair‐stand tests after vitamin D supplementation. This finding remained significant after controlling for potential confounding variables. There was also an inverse correlation between serum 25(OH)D levels and fat mass index (FMI) among women, suggesting that higher supplementation with vitamin D is needed as weight increases. The results of this study suggest that supplementation with vitamin D may be most beneficial in older populations who have low baseline physical functioning. © 2013 American Society for Bone and Mineral Research.