Vertebral fractures, trabecular bone score and their determinants in chronic hypoparathyroidism.

PURPOSE: Patients with hypoparathyroidism are at risk of vertebral fractures (VFs) despite high bone mineral density (BMD). We investigated this paradox by assessing trabecular bone score (TBS) and hip structural analysis (HSA) in non-surgical chronic hypoparathyroidism (cHypoPT) with and without VFs. METHODS: 152 cHypoPT patients (age 40.2 ± 13.4 years, M: F = 81:71) with a median follow-up of 8 (2-13) years were assessed for BMD, VFs, TBS, and HSA and compared with 152 healthy controls. VFs at T7-L4 were assessed by Genant's method. Average serum total calcium and phosphorus during follow-up were assessed. RESULTS: The lumbar spine and hip BMD were higher by 25.4 and 13.4% in cHypoPT than controls (P < 0.001). Paradoxically, VFs (30.9 vs.7.9%), including multiple (12.5 vs. 2.6%) were higher in cHypoPT (P < 0.001). Though overall average TBS (1.411 ± 0.091) was normal in cHypoPT, 25.4% of the females had subnormal TBS, more in post than pre-menopausal women (52.3 vs. 14%, P = 0.002) and as compared to males (6.1%, P = 0.001). TBS correlated with menopausal status and follow-up serum calcium-phosphorus product. For every gm/cm2 rise in BMD, TBS increase was only 0.227 in cHypoPT compared to 0.513 in controls. Frequency of VFs increased with declining TBS (P = 0.004). HSA was comparable between cHypoPT with and without VFs. 23.4% of cHypoPT with VFs had subnormal TBS. CONCLUSION: 31% of cHypoPT patients had VFs. TBS indicated degraded bone microarchitecture in 50% of the post-menopausal cHypoPT women. However, TBS has limitations to detect abnormal bone microarchitecture in cHypoPT as only one-fourth of patients with VFs showed low TBS.

Effect of vitamin D supplementation on cathelicidin, IFN-γ, IL-4 and Th1/Th2 transcription factors in young healthy females.

OBJECTIVES: We assessed the effect of cholecalciferol and calcium supplementation on mRNA expression of cathelicidin (LL-37), Th1 and Th2 cytokines and their transcription factors in the peripheral blood mononuclear cells (PBMCs) in healthy females with vitamin D deficiency (VDD). SUBJECTS/METHODS: Subjects included 131 females with biochemical VDD randomized to receive (a) oral cholecalciferol (60,000 IU/week for 8 weeks followed by 60,000 IU/fortnight (b) calcium (elemental calcium 500 mg twice/day) (c), dual supplementation and (d) placebo for 6 months. The mRNA expression of cathelicidin, Th1 (IFN-γ) and Th2 (IL-4 and its antagonist-IL-4δ2) cytokines and their transcription factors (T-bet, STAT4, GATA-3, STAT6) were measured in the PBMC by real-time PCR before and after intervention. RESULTS: Cholecalciferol-supplemented groups showed significant rise of mean serum 25(OH)D (30.6 ± 7.51 and 28.6 ± 8.41 ng/ml). The expression of LL-37, IFN-γ, IL-4, IL-4δ2 and transcription factors were comparable in the four groups at baseline. Despite significant increase in mean serum 25(OH)D in the cholecalciferol-supplemented groups, their mean mRNA transcripts of LL-37, IFN-γ, IL-4, transcription factors and their IFN-γ/IL-4 and T-bet/GATA-3 ratios were similar to that of calcium and placebo groups. CONCLUSIONS: Six months of cholecalciferol/calcium supplementation in young females with VDD do not lead to significant alteration in mRNA expression of LL-37, Th1/Th2 cytokines and their transcription factors.

Risk and outcome of multidrug-resistant tuberculosis: vitamin D receptor polymorphisms and serum 25(OH)D.

SETTING: All India Institute of Medical Sciences and Rajan Babu Institute of Pulmonary Medicine and Tuberculosis, New Delhi, India. OBJECTIVE: To investigate the association of vitamin D receptor (VDR) polymorphisms and serum 25(OH)D with susceptibility to, and response to treatment of, multidrug-resistant tuberculosis (MDR-TB) in comparison with drug-susceptible pulmonary TB (DS-PTB) and healthy controls. DESIGN: Cross-sectional study. METHODS: A total of 897 participants from northern India were consecutively enrolled into three groups (MDR-TB 354, DS-PTB 338, controls 205). Genotypic and allelic frequencies of FokI, BsmI and TaqI VDR polymorphisms, and serum 25(OH)D, calcium and intact parathyroid hormone were measured in all participants. In those with active TB, disease severity, time to sputum smear and culture conversion were correlated with VDR genotype and biochemical parameters. RESULTS: FokI Ff genotype and TaqI t allele correlated positively with MDR-TB; Ff genotype and f allele of FokI frequency were higher in both TB groups. BsmI Bb genotype correlated inversely with MDR-TB. Serum 25(OH)D concentrations were significantly lowest in MDR-TB, correlating inversely with time to sputum smear conversion. CONCLUSIONS: VDR gene polymorphisms and hypovitaminosis D may predispose to MDR-TB. Lower serum 25(OH)D may increase time to MDR-TB sputum smear negativity.

Presence of impaired intestinal calcium absorption in chronic hypovitaminosis D and its change after cholecalciferol supplementation: assessment by the calcium load test.

BACKGROUND: Hypovitaminosis D is common in Asian Indians and its functional significance is currently under investigation. Previous studies have reported on the effect of low serum 25(OH)D levels (<50 nmol L(-1)) on bone mineral density and serum parathyroid hormone values. The present study assessed the effect of chronic hypovitaminosis D in Asian Indians on intestinal calcium absorption and its change after cholecalciferol supplementation. METHODS: Subjects included 29 healthy volunteers [mean (SD) age, 28.4 +/- 6.4 years] with low serum 25(OH)D levels on screening. Intestinal calcium absorption was assessed by the 'calcium load test' with 1 g of oral elemental calcium. Subjects were put on a calcium restricted diet 1 week prior to the test. The calcium load test was repeated in 26 of them after 8 weeks of supplementation with oral cholecalciferol (60 000 IU week(-1)). RESULTS: The mean urinary calcium/creatinine ratio of the study subjects was 0.027 +/- 0.023 mg mg(-1) under fasting conditions and increased to 0.035 +/- 0.032 mg mg(-1) after calcium loading (delta change = 29.6%, P = 0.33). After 8 weeks of cholecalciferol supplementation, the mean serum 25(OH)D increased from 18.9 +/- 11.9 to 84.4 +/- 34.9 nmol L(-1) (P < 0.0001). Concomitantly, the mean urinary calcium/creatinine ratio of the study subjects increased from 0.030 +/- 0.024 mg mg(-1) under fasting conditions to 0.059 +/- 0.045 mg mg(-1) after calcium loading (delta change = 96.6%, P = 0.008). CONCLUSIONS: The results obtained in the present study show that chronic hypovitaminosis D in Asian Indians has functional relevance in terms of its effect on intestinal calcium absorption, which improves with cholecalciferol supplementation. These findings support the need for improving the vitamin D status of Asian Indians through dietary supplementation and exposure to sunshine.

Presence of 25(OH)D deficiency and its effect on vitamin D receptor mRNA expression.

BACKGROUND AND OBJECTIVES: Vitamin D and its metabolites act through vitamin D receptor (VDR). We hypothesized that subjects with low serum 25(OH)D levels but normal PTH might have increased VDR expression. DESIGN AND METHODS: VDRmRNA expression was assessed by real time PCR in duodenal mucosa and PBMC (peripheral blood mononuclear cells) in 45 subjects with normal duodenoscopy and in PBMC alone in 48 healthy volunteers with hypovitaminosis D. 25(OH)D, PTH and VDRmRNA expression in PBMC was reassessed after 8 weeks of oral cholecalciferol (60 000 IU per week) in a subset (n=23) of healthy volunteers. RESULTS AND CONCLUSIONS: The VDRmRNA expressions in the duodenum and PBMC were significantly correlated (r=0.42), but the expression was 13 times higher in the former than the latter. The mean VDRmRNA expression was similar in 25(OH)D-deficient subjects with or without PTH elevation, both in the duodenum and PBMC. The PBMC VDRmRNA expression showed no significant change after cholecalciferol supplementation. A weak correlation coefficient between duodenal mucosa and PBMC VDRmRNA suggests that caution needs to be exercised while using the latter as a surrogate for other sites.

Reversible peripheral neuropathy in idiopathic hypoparathyroidism.

We describe a 40-year-old male with idiopathic hypoparathyroidism presenting with tetany, proximal weakness, signs of hypocalcaemia including Chvostek and Trousseau's and diminished tendon reflexes in the upper and lower limbs. Electrophysiological studies revealed a sensory-motor neuropathy, predominantly axonal as evidenced by decreased CMAP amplitudes, with normal distal latencies-velocites, except for median nerve where a prolonged distal latency was observed. Serial nerve conduction studies were performed at repeated intervals for 2 years, while he received treatment for hypoparathyroidism (calcium and vitamin D supplementation). A progressive improvement in neuropathy both clinical and on electrophysiological studies was observed. Occurrence of peripheral neuropathy in hypocalcaemic states such as hypoparathyroidism and its reversibility after normalization of calcium homeostasis lend proof to the role of critical Ca2+ ion concentration in the normal functioning of the peripheral axons.

Circadian desynchronization in pulse rate, systolic and diastolic blood pressure, rectal temperature and urine output in traumatic tetraplegics.

An investigation was undertaken to study the circadian rhythmicity in pulse rate, systolic and diastolic blood pressure, rectal temperature and urine output in eight traumatic tetraplegics in view of the fact that diurnal rhythmicity in prolactin response to thyrotropin-releasing hormone was absent in such patients. The data, analysed by single cosinor procedure, showed absence of rhythmicity in all five parameters. Analysis of variance also showed no significant difference in these parameters at various time points. Knowledge of the alterations in circadian biology subsequent to cervical spinal cord trauma would provide useful guidelines towards chronotherapy and vocational rehabilitation of tetraplegics besides possible restoration of euchronism by pharmacological means.