A 45-year-old woman is evaluated 2 weeks after she fractured her left radius during a fall from standing height. Two months previously, she passed a renal stone. There is no family history of osteoporosis or hypercalcemia. Physical examination is unremarkable. Serum laboratory results are as follows: Bone density testing performed using dual-energy x-ray absorptiometry reveals osteoporosis. Which of the following is the major contributor to bone loss in this patient?

Question

A 45-year-old woman is evaluated 2 weeks after she fractured her left radius during a fall from standing height.  Two months previously, she passed a renal stone.  There is no family history of osteoporosis or hypercalcemia.  Physical examination is unremarkable.  Serum laboratory results are as follows:  Bone density testing performed using dual-energy x-ray absorptiometry reveals osteoporosis.  Which of the following is the major contributor to bone loss in this patient?

Quizplus · Accepted Answer

11ec160b_3abb_7e91_9249_91e64cd63fe6_MD0001_00 This patient has hyperparathyroidism, presenting with osteoporosis and nephrolithiasis associated with mild hypercalcemia and an inappropriately elevated parathyroid hormone (PTH) level. PTH increases bone turnover by stimulating the differentiation and activity of osteoblasts, leading to increased bone formation. In addition, PTH upregulates the expression of receptor activator of nuclear factor kappa B ligand (RANK-L) on the surface of the activated osteoblasts, which binds RANK on nearby osteoclast precursor cells and induces maturation to active osteoclasts. Therefore, PTH causes bone formation (by direct effect on osteoblasts) and bone resorption (by paracrine effect on osteoclasts). Bone turnover is normally balanced, with bone formation proportionate to resorption. In hyperparathyroid states, continuous exposure to high PTH levels cause increased RANK-L expression along with suppression of osteoprotegerin (a counterregulatory decoy receptor). This leads to greater bone resorption than formation and net bone loss. (Choices A and D) PTH upregulates 1-alpha-hydroxylase in the kidneys, which leads to increased (not decreased) conversion of 25-hydroxyvitamin D (calcidiol) to 1,25-dihydroxyvitamin D (calcitriol). Calcitriol subsequently induces increased (not decreased) intestinal calcium absorption. (Choice B) PTH increases renal reabsorption of calcium. Despite this, hypercalciuria is common in hyperparathyroidism because the filtered calcium load may exceed renal reabsorption capacity. However, the local concentrations of calcium in the bone remain elevated, and urinary calcium wasting is not a major contributor to bone loss. (Choice C) Supraphysiologic glucocorticoid (eg, prednisone) doses can cause osteoporosis, in part due to decreased proliferation and differentiation of osteoblast precursor cells. PTH increases the differentiation of osteoblast precursors; osteoporosis occurs in hyperparathyroidism because of a proportionally greater increase in osteoclast activity. Educational objective: Parathyroid hormone directly stimulates osteoblasts, leading to increased bone formation. Expression of RANK-L on osteoblasts induces increased bone resorption via a paracrine effect on nearby osteoclasts. Hyperparathyroidism causes increased RANK-L expression and decreased expression of osteoprotegerin, leading to net bone loss.

A 45-Year-Old Woman Is Evaluated 2 Weeks After She Fractured