Secondary Hyperparathyroidism Blunts Benefits of Bisphosphonates

From the American Society for Bone and Mineral Research Assess PTH Levels Before Prescribing these Drugs

PHILADELPHIA—The millions of patients who take bisphosphonates to treat osteoporosis may not be deriving the full benefits from these agents because of vitamin D deficiency, according to data presented at the American Society for Bone and Mineral Research annual meeting.

This study investigated the effects of persistent secondary hyperparathyroidism on bone mineral density (BMD) in postmenopausal women receiving >1 year of alendronate (Fosamax) for osteopenia/osteoporosis.

Included were 95 community-dwelling ambulatory women ≥60 years old with lower spine, femoral neck, or total hip T scores ≤2.5; all had hyperparathyroidism (parathyroid hormone [PTH] >65 pg/mL) secondary to vitamin D deficiency. They were randomized to receive calcitriol (Rocaltrol) 0.5 μg/day (n = 48) or placebo (n = 47); all participants took alendronate 70 mg/ week plus a calcium supplement to maintain their daily intake at 1500 mg.

After 1 year, lower spine BMD increased in both groups, but the increase in the calcitriol group was approximately double that of the placebo group (6.8% vs 3.7%; P = .001). At 1 year, changes in spine BMD correlated with reductions in PTH levels (P = .022) in those receiving calcitriol. Regardless of which group they were assigned to, “patients with normalized PTH at the end of follow-up had a higher response of [spine] BMD,” said lead investigator Andrea Giusti, MD, medical director, Department of Gerontology and Musculoskeletal Science, Galliera Hospital, Genoa, Italy.

He said that serum PTH levels fell 22.1% from baseline in the calcitriol group (P <.001), but levels did not change significantly in the placebo group (—3.7%, P = .132; calcitriol group vs placebo group, P <.001).

More than three fourths (78%) of those taking calcitriol achieved normal PTH levels compared with 31% of those taking placebo.

Total hip and femoral neck BMD increases ranged from 1.5% to 3.2% and did not significantly differ from baseline or between groups.

Dr Giusti explained that secondary hyperparathyroidism diminishes the effects of alendronate on BMD, noting that normalizing PTH levels with calcitriol allowed increases in spine BMD similar to those seen in clinical trials of the drug.

About half of the elderly patients referred to his healthcare center have secondary hyperparathyroidism related to vitamin D deficiency, Dr Giusti said. The condition is prevalent among European elderly, varying from 15% to 18%, depending on the setting. But evidence suggests that hypovitaminosis D affects all community-dwelling older adults, regardless of latitude.

&#8220;In patients over 65 years, it is a real big problem—low level of vitamin D and high PTH,&#8221; Dr Giusti says. Contributing factors are low vitamin D intake, lack of sun exposure, possibly a defect in the skin, and decreased hydroxylation to the active form in the kidney. He adds that a high PTH level may be a marker for frailty in the elderly, since it is related to falls, fractures, and sarcopenia.

He agrees that calcitriol is an expensive treatment and that in daily practice, 25-hydroxyvitamin D may be a more practical solution for secondary hyperparathyroidism. He is now interested in determining the best form of vitamin D for quickly normalizing PTH levels.

&#8220;Current guidelines do not suggest evaluating PTH levels before giving alendronate or other such bisphosphonates,&#8221; Dr Giusti says. While he does not recommend universal screening, he suggests that physicians test patients >65 years with osteoporosis before initiating treatment with a bisphosphonate.