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.

Keywords: bisphosphonates; bone markers; bone mineral density; calcimimetics; histomorphometry; osteitis fibrosa cystica; parathyroid hormone; parathyroidectomy.

Figure 1.

Effects of parathyroid hormone (PTH) on bone cells. The anabolic effects are indicated by the red lines and highlighted by the red shadow, while the catabolic effects are indicated in black and highlighted by the grey shadow (‘+’ = stimulation; ‘–’ = inhibition). See text for details. OPG, osteoprotegerin; RANKL, receptor activator of nuclear factor κB ligand.

Figure 2.

Baseline levels of serum bone alkaline phosphatase (BALP) and serum carboxy-terminal collagen crosslinks (S-CTX) in both sexes in a series of patients with primary hyperparathyroidism selected for parathyroidectomy (women in gray, men in black); normal range is indicated between or below the dashed lines.

Figure 3.

Long bone X-rays of a patient with severe primary hyperparathyroidism and osteitis fibrosa cystica. Arrows indicate brown tumors.

Figure 4.

Rate of vertebral fractures (evaluated by dual-emission X-ray absorptiometry) in patients with primary hyperparathyroidism and controls. Left panel: symptomatic and asymptomatic patients and controls. Right panel: asymptomatic patients, grouped according to whether they met or did not meet the criteria for surgery established by the 2002 Workshop on Asymptomatic Primary Hyperparathyroidism [Bilezikian et al. 2002], and controls. P value refers to the odds ratio between different groups. (Reproduced from Vignali et al. [2009] with permission, Copyright 2009, The Endocrine Society.)

Figure 5.

Mean (±SEM) change (% of basal) in lumbar spine (A), total hip (B) and distal one-third of the radius (C) bone mineral density (BMD) in patients with mild primary hyperparathyroidism randomized to parathyroidectomy (Ptx) or followed without intervention (no PTx). *p = 0.0005; **p = 0.0002; ^p = 0.003; ^^p = 0.0001. (Reproduced from Ambrogini et al. [2007] with permission, Copyright 2007, The Endocrine Society.)