Bone disease in primary hyperparathyrodism

Abstract

Nowadays, primary hyperparathyroidism (PHPT) is mostly a mild disease. Overt skeletal manifestations are rare but decreased bone mineral density (BMD) can still be demonstrated. Even in mild cases, excess parathyroid hormone (PTH) increases bone turnover leading to bone loss particularly at cortical sites. Conversely, a relative preservation of cancellous bone has been shown by histomorphometric analyses and advanced imaging techniques. An increased fracture rate has been demonstrated in untreated patients with PHPT at peripheral sites and in the spine. Parathyroidectomy (PTx) is the definitive cure for PHPT. With the restoration of normal PTH, bone resorption is quickly tapered down, while bone formation proceeds at the level of bone multicellular units, which were activated prior to PTx. The rapid refilling of the enlarged remodeling space and the subsequent matrix mineralization will result in an increase in BMD at sites rich in trabecular bone, such as lumbar spine and hip, which mainly occurs during the first 6–12 months after PTx. Cortical bone is less responsive to PTX because of the low rate of bone turnover, but sensible increases in BMD at the distal third of the radius can be observed in the long term. PTx seems to decrease the risk of fractures but more data are needed before a definitive conclusion on this important matter can be reached. Treatment with bisphosphonates can be considered for patients with low BMD who do not undergo PTx. Two-year treatment with alendronate has been shown to decrease bone turnover markers and increase BMD at the lumbar spine and hip, but not at the distal radius. Cinacalcet stably decreased serum calcium levels across a broad range of PHPT severity, but no change in BMD occurred in patients treated for up to 5.5 years.