Alendronate in Primary Hyperparathyroidism: A Double-Blind, Randomized, Placebo-Controlled Trial

Abstract

Primary hyperparathyroidism (PHPT) is often associated with reduced bone mineral density (BMD). A randomized, double-blind, placebo-controlled trial was conducted to determine whether alendronate (ALN), 10 mg daily, maintains or improves BMD in patients with PHPT. Eligible patients had asymptomatic PHPT and did not meet surgical guidelines or refused surgery. Forty-four patients randomized to placebo or active treatment arms were stratified for gender. At 12 months, patients taking placebo crossed over to active treatment. All patients were on active treatment in yr 2. The primary outcome index, BMD, at the lumbar spine (LS), femoral neck, total hip, and distal one third radius was measured every 6 months by dual-energy x-ray absorptiometry. Calcium, phosphorous, PTH, bone-specific alkaline phosphatase (BSAP) activity, urinary calcium, and urinary N-telopeptide (NTX) excretion were monitored every 3 months. Treatment with alendronate over 2 yr was associated with a significant (6.85%; micro(d) = 0.052; +/-0.94% se; P < 0.001) increase in LS BMD in comparison with baseline. Total hip BMD increased significantly at 12 months with alendronate by 4.01% (micro(d) = 0.027; +/-0.77% se; P < 0.001) from baseline and remained stable over the next 12 months of therapy. BMD at the one third radius site did not show any statistically significant change in the alendronate-treated group at 12 or 24 months of therapy. At 24 months, the alendronate-treated group showed a 3.67% (micro(d) = 0.022; +/-1.63% se; P = 0.038) gain in bone density at the femoral neck site in comparison with baseline. The placebo group, when crossed over to alendronate at 12 months, showed a significant change of 4.1% (micro(d) = 0.034; +/-1.12% se; P = 0.003) in the LS BMD and 1.7% (micro(d) = 0.012; +/-0.81% se; P = 0.009) at the total hip site in comparison with baseline. There was no statistically significant change seen in the placebo group at 12 months at any BMD site and no significant change at 24 months for the distal one third radius or femoral neck sites. Alendronate was associated with marked reductions in bone turnover markers with rapid decreases in urinary NTX excretion by 66% (micro(d) = -60.27; +/-13.5% se; P < 0.001) at 3 months and decreases in BSAP by 49% at 6 months (micro(d) = -15.98; +/-6.32% se; P < 0.001) and by 53% at 9 and 12 months (micro(d) = -17.11; +/-7.85% se; P < 0.001; micro(d) = -17.36; +/-6.96% se; P < 0.001, respectively) of therapy. In the placebo group, NTX and BSAP levels remained elevated. Serum calcium (total and ionized), PTH, and urine calcium did not change with alendronate therapy. In PHPT, alendronate significantly increases BMD at the LS at 12 and 24 months from baseline values. Significant reductions in bone turnover occur with stable serum calcium and PTH levels. Alendronate may be a useful alternative to parathyroidectomy in asymptomatic PHPT among those with low BMD.

Diagnosis and management of primary hyperparathyroidism: a scientific statement from the Department of Bone Metabolism, the Brazilian Society for Endocrinology and Metabolism

“…After 1 year, patients receiving placebo, started on alendronate and similar changes in BMD were observed in the 2 nd year. Bone turnover markers decreased with the use of alendronate and serum PTH, phosphate and ionized calcium levels did not change during the study (171) (A-1B).…”

“…Data from randomized controlled studies have consistently demonstrated that oral alendronate decreases bone turnover and increases BMD in patients with mild PHPT, although the effects on serum calcium have been inconsistent (169)(170)(171) (A-1B).…”

Is surgery necessary for ‘mild’ or ‘asymptomatic’ hyperparathyroidism?

“…They also slightly increase the bone mineral density parameters at the lumbar spine and hip but not at the distal radius. Their possible long-term disadvantages must not be overlooked (62,63,64).…”

Normocalcemic Primary Hyperparathyroidism

“…Unfortunatelly, none of this treatment have been evaluated in clinical assays neither in hyperparathyroidism nor HPHPT ). Only alendronate treatment was shown to improve BMD in lumbar spine of patients with primary hyperparthyroidism without changes in calcium levels to a degree comparable both to their effects in eucalcemic populations (Khan et al, 2004) What is more, fracture outcome date are not available until now with any of the treatments evaluated.…”