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Alendronate Suppresses the Beneficial Effects of Parathyroid Hormone Therapy in Men with Osteoporosis

The addition of alendronate to parathyroid hormone treatment in men with osteoporosis curbs the significant increases in bone mineral density and serum alkaline phosphatase levels observed with parathyroid hormone therapy alone, say researchers.

Alendronate is an antiresorptive bisphosphonate therapy that can increase bone mineral density and decrease the risk of fracture in patients with osteoporosis. Parathyroid hormone therapy is another treatment option for men and oestrogen-deficient women with osteoporosis, as this treatment has been shown to increase bone mineral density in these patients.

Unlike the bisphosphonates, parathyroid hormone therapy increases both bone formation and bone resorption. It has therefore been suggested that combining parathyroid hormone therapy with the antiresorptive properties of alendronate may increase the benefits of parathyroid hormone therapy alone.

Joel S. Finkelstein, MD, and colleagues at the Massachusetts General Hospital, Boston, United States, evaluated the use of alendronate and parathyroid hormone, alone and in combination, in the treatment of osteoporosis in men.

The randomised study included 83 men (average age 58) with low bone mineral density that received either alendronate (10 mg daily), parathyroid hormone (40 ug subcutaneously daily), or combinatorial therapy for 30 months. Notably, parathyroid hormone therapy was not initiated until the sixth month of the study.

Bone mineral density of the lumbar spine, proximal femur, radial shaft, and total body was measured by dual-energy x-ray absorptiometry every 6 months. Serum alkaline phosphatase levels were also measured at these times.

Overall, bone mineral density in the lumbar spine and femoral neck increased significantly higher in those treated with parathyroid hormone alone than in those given alendronate alone. Furthermore, combinatorial therapy also showed greater effects on bone mineral density than alendronate alone.

Interestingly, parathyroid hormone therapy alone was more effective at increasing bone mineral density than combinatorial therapy, indicating that the addition of alendronate actually suppressed parathyroid hormone therapy's beneficial effects.

Results also indicated that serum alkaline phosphatase levels increased significantly in patients receiving only parathyroid hormone therapy. In contrast, levels decreased in the alendronate alone group and remained steady in the combination group after 12 months.

Reports of headache, dizziness, and joint pain were significantly higher in patients receiving parathyroid hormone therapy as compared to those receiving only alendronate. Furthermore, significantly more men receiving parathyroid hormone therapy discontinued the study, the most common reason being discomfort or inconvenience related to injections.

The authors conclude that "alendronate impairs the ability of parathyroid hormone to increase bone mineral density at the lumbar spine and femoral neck in men with osteoporosis." They further note that "additional studies are needed before combinations of antiresorptive agents and parathyroid hormone can be recommended for the treatment of men with osteoporosis."


N Engl J Med 2003 Sep 25;349:13:1216-26. "The Effects of Parathyroid Hormone, Alendronate, or Both in Men with Osteoporosis"

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