Osteoporosis in Multiple Endocrine Neoplasia Type 1: Severity, Clinical Significance, Relationship to Primary Hyperparathyroidism, and Response to Parathyroidectomy

Background: Sporadic primary hyperparathyroidism (PHPT) occurs most frequently in postmenopausal women. Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal-dominant disease in which mild to moderate PHPT develops in most gene carriers by 20 years of age. Primary hyperparathyroidism associated with MEN I is typically recurrent, despite initially successful subtotal parathyroidectomy. Osteoporosis is considered a complication of sporadic PHPT and an indication for parathyroidectomy. In the setting of MEN 1, however, the relationship of bone mass to PHPT, fracture risk, and parathyroidectomy is unknown. Hypothesis: Parathyroidectomy improves bone mineral density for patients with primary hyperparathyroidism in the setting of MEN 1. Design: Case series. Setting: Tertiary referral center. Patients: Twenty-nine women with MEN 1 belonging to a single family with a history of MEN 1. Interventions: Parathyroidectomy. Main Outcome Measures: Bone mineral density (BMD) and history of skeletal fracture. Results: Osteopenia and osteoporosis were diagnosed in 41% and 45% of patients, respectively. Forty- four percent of patients with uncontrolled PHPT had severe osteopenia (T score, <-2.0) by 35 years of age. Reduction in BMD was greatest at the femoral neck. Reduced BMD was associated with an increased likelihood of skeletal fracture (P = .05). Patients with uncontrolled PHPT had lower femoral neck and lumbar spine BMDs than those in whom PHPT was controlled by parathyroidectomy (P = .005 and .02, respectively). Successful parathyroidectomy improved femoral neck and lumbar spine BMDs by a mean ± SEM of 5.2% ± 2.5% and 3.2% ± 2.9%, respectively. Conclusions: Osteoporosis is a frequent and early complication of PHPT in MEN 1. Despite difficulty in achieving a cure of PHPT in MEN 1, parathyroidectomy has an important role in the optimization of BMD for patients with MEN 1.