Combination Teriparatide and Raloxifene Therapy for Postmenopausal Osteoporosis: Results From a 6-Month Double-Blind Placebo-Controlled Trial

Authors


  • Data previously presented at the 26th Annual Meeting of American Society for Bone and Mineral Research in Seattle, WA, October 1–5, 2004, the 68th Annual Scientific Meeting of the American College of Rheumatology in San Antonio, TX, October 17–21, 2004, and the 2nd Joint Meeting of the International Bone and Mineral Society (IBMS) and the European Society for Calcified Tissue (ECTS) in Geneva, Switzerland, June 25–29, 2005.

  • Drs Chad Deal and Molly Omizo are consultants for Eli Lilly. Elliott Schwartz is a consultant for Eli Lilly, Merck, Procter and Gamble, Aventis, Pfizer, Amgen, Novartis, NPS Pharmaceuticals, Pharmacia, and Wyeth. Dr Erik Eriksen held a previous corporate appointment at Eli Lilly and owns stock in Eli Lilly and Company. Dr Emmett V Glass is an employee of Eli Lilly. Drs Per Cantor, Jingyuan Wang, Stephen L Myers, and John H Krege are employees of Eli Lilly and own stock in Eli Lilly and Company.

Abstract

We compared combination treatment with teriparatide plus raloxifene with teriparatide alone in women with postmenopausal osteoporosis in a 6-month double-blind, placebo-controlled trial that measured biochemical markers of bone turnover and BMD. Markers of bone formation and spine BMD increased similarly with teriparatide alone and combination therapy. However, combination therapy induced a significantly smaller increase in bone resorption versus teriparatide alone and significantly increased total hip BMD versus baseline.

Introduction: The effects of combining two approved treatments for osteoporosis with different modes of action were examined by comparing teriparatide [rhPTH(1–34)] monotherapy with combination teriparatide and raloxifene therapy.

Materials and Methods: A 6-month randomized, double-blind trial comparing teriparatide plus raloxifene (n = 69) versus teriparatide plus placebo (n = 68) was conducted in postmenopausal women with osteoporosis.

Results: Bone formation (N-terminal propeptide of type 1 collagen [PINP]) increased similarly in both treatment groups. However, the increase in bone resorption (serum C-terminal telopeptide of type I collagen [CTx]) in the combination group was significantly smaller than in the teriparatide-alone group (p = 0.015). Lumbar spine BMD significantly increased 5.19 ± 0.67% from baseline in the teriparatide-alone group. In the combination group, lumbar spine (6.19 ± 0.65%), femoral neck (2.23 ± 0.64%), and total hip (2.31 ± 0.56%) BMD significantly increased from baseline to study endpoint, and the increase in total hip BMD was significantly greater than in the teriparatide-alone group (p = 0.04). In the teriparatide-alone group, mean serum calcium levels increased from baseline to endpoint (0.30 ± 0.06 mg/dl, p < 0.001), whereas mean serum phosphate remained unchanged. In the combination group, mean serum calcium was unchanged, and mean serum phosphate decreased (−0.20 ± 0.06 mg/dl, p < 0.001) from baseline to endpoint. Changes in serum calcium (p < 0.001) and phosphate (p < 0.004) were significantly different between treatment groups. The safety profile of combination therapy was similar to teriparatide alone.

Conclusions: Combination therapy increased bone formation to a similar degree as teriparatide alone. However, the increase in bone resorption was significantly less and total hip BMD significantly increased for combination therapy compared with teriparatide alone. Combination treatment with raloxifene may thus enhance the bone forming effects of teriparatide. Further studies over longer treatment duration that include fracture endpoints are necessary to fully ascertain the clinical significance of combination raloxifene plus teriparatide therapy in postmenopausal osteoporosis.

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