A 40-year-old developed pathological fractures and was found to be having low bone density after a Dexa Scan. Laboratory tests show low plasma calcium, elevated PTH levels, and low vitamin D levels. The patient is on a balanced diet. However, the patient's plasma creatinine and urea are elevated markedly. Which of the following is the most likely reason for the hypocalcemia and reduced bone mass?: (A) Excessive urinary excretion of calcium, (B) Impaired secretion of calcitonin, (C) A parathyroid gland tumor generating excessive amounts of PTH, (D) Reduced renal activity of 1 alpha-hydroxylase activity
Answer is D. Here there are signs of early renal failure. This reduces the levels of 1 alpha-hydroxylase in the proximal tubule cells, thereby reducing the conversion of 25-hydroxyvitamin D, the inactive form of vitamin D, to 1,25-dihydroxyvitamin D, the most active form. The 25-hydroxycholecalciferol is conveed in the cells of the proximal tubules of the kidneys to the more active metabolite 1,25-dihydroxycholecalciferol, which is also called calcitriol or 1,25-(OH)2D3. 1,25-Dihydroxycholecalciferol is also made in the placenta, in keratinocytes in the skin, and in macrophages. Ref: Barrett K.E., Barman S.M., Boitano S., Brooks H.L. (2012). Chapter 21. Hormonal Control of Calcium & Phosphate Metabolism & the Physiology of Bone. In K.E. Barrett, S.M. Barman, S. Boitano, H.L. Brooks (Eds), Ganong's Review of Medical Physiology, 24e.