SUN-512 Denosumab Improves Trabecular but Not Cortical Bone Osteoporosis in a Patient with Refractory Primary Hyperparathyroidism

Background: Primary hyperparathyroidism is a disorder of parathyroid glands in which one or more of these glands is/are overactive. As a result, the overactive gland releases too much parathyroid hormone (PTH) which increases serum calcium levels from thinning of the bones. Osteoporosis occurs in patients with hyperparathyroidism, but it is usually reversible post parathyroidectomy. In the United States, about 100,000 people develop primary hyperparathyroidism each year. The disorder is diagnosed most often in people between age 50 and 60, and women are affected about three times as often as men. Case: This is the case of a 71-year-old lady with history of primary hyperparathyroidism treated with left parathyroidectomy for severe hypercalcemia and osteoporosis. However, although quiescent for few months, the hyperparathyroidism recurred and the osteoporosis worsened. She was referred to our Osteoporosis clinic for evaluation and management. Patient had multiple Sestamibi scans for re-localization of the abnormal parathyroid which were all unsuccessful. Also, she went through a second neck exploration which failed to find the abnormal parathyroid gland. She even underwent fine needle aspiration of intrathyroidal cysts with PTH washouts for identification of possible parathyroid adenoma with negative results. Patient was then treated with bisphosphonates for 5 years and her DEXA scan T score of (-) 2.9 at the radius never improved. Bisphosphonates were discontinued, and patient was treated with Denosumab infusions every 6 months for the last two years in an attempt to help with both osteoporosis and hypercalcemia. Repeated DEXA scan revealed significant improvement of bone mineral density at the level of the lumbar spine, with worsening of osteoporosis at the femurs and radius. Hypercalcemia normalized while PTH remained inappropriately high normal. Discussion: Osteoporosis from hyperparathyroidism affects predominantly long bones. Aside from parathyroidectomy of parathyroid adenomas, no other therapy has been shown to improve cortical bone osteoporosis due to hyperparathyroidism. Denosumab is a human monoclonal antibody which is used for the treatment of osteoporosis in postmenopausal women who have high risk of bone fracture. It has been used lately also for treatment of hypercalcemia of malignancy. Although our patient’s hypercalcemia and trabecular bone osteoporosis improved with Denosumab, cortical bone osteoporosis worsened. This case illustrates the power of continuous PTH secretion on cortical bone resorption which is able to counteract the beneficial effect of Rank ligand blockade at the trabecular bone level. It also demonstrates the need for more research on potential therapies to address this PTH specific action.