Vitamin D Deficiency in Primary Hyperparathyroidism

DESCRIPTION (provided by applicant): Vitamin D deficiency or insufficiency is more common in primary hyperparathyroidism (PHPT) than in the general population. Clinical manifestations of PHPT are more severe in vitamin D deficient patients, and even in those with mild disease, patients with low vitamin D levels have higher PTH concentrations and bone turnover markers. Given the frequency of vitamin D deficiency in the PHPT population, it is likely that our current understanding of the biochemical and skeletal features of PHPT reflects an admixture of these two conditions. The central hypotheses of this proposal are that in patients with PHPT: 1) Vitamin D deficiency worsens the hyperparathyroid state and is associated with its own specific skeletal features; and 2) Repletion of vitamin D will ameliorate those aspects of the disease that are due to vitamin D deficiency, and thus reveal the true biochemical and skeletal phenotype of the underlying disease. To test these hypotheses, this proposal will utilize state-of-the-art biochemical and skeletal imaging methods. The proposal has the following aims: 1. To compare PHPT patients with and without vitamin D deficiency in order to: a) determine the skeletal features of the hyperparathyroid state that are attributable to vitamin D deficiency; and b) to describe the skeleton in PHPT without the confounding effects of co- existing vitamin D deficiency. 2. To investigate the early effects of high dose vitamin D repletion on histomorphometric parameters of bone remodeling (by quadruple labeled bone biopsy). 3. To investigate the effects of three vitamin D repletion regimens on biochemical, denstometric, microarchitectural and biomechanical features of PHPT. This proposal will fulfill a key mandate of the Third International Workshop on Asymptomatic Primary Hyperparathyroidism (2008) to obtain more data on vitamin D deficiency in individuals with PHPT. The recently published International Consensus Guidelines on Asymptomatic PHPT (J Clin Endocrinol Metab 94:335-9, 2009) specifically call for measurement of 25- hydroxyvitamin D in all patients with PHPT, and repletion of low levels (