Menopause Live - IMS Updates

Date of release: 29 March, 2010

Combining therapies for osteoporosis

A new study on teriparatide (a PTH analogue) and alendronate brings again to clinical attention the issue of combination therapies for osteoporosis. The study by Finkelstein and colleagues [1] randomized 93 postmenopausal women with low bone mineral density (BMD) to either teriparatide 40 μg subcutaneously daily, or alendronate 10 mg daily, or both for 30 months. Teriparatide was begun at month 6 (thus treatment lasted 24 months according to the approved duration by the FDA). The mean age at baseline was around 63 years, and the mean lumbar spine and femoral T-score was around -2 standard deviations. The spine BMD increased by 6.8 ± 4% in women treated with alendronate, by 17.8 ± 11% in women treated with teriparatide, and by 11.9 ± 9% in women treated with both medications. The corresponding percentages for the femoral neck were 3.5 ± 4%, 10.8 ± 5% and 3.1 ± 5%, respectively. Levels of serum osteocalcin and N-terminal propeptide of type 1 collagen (P1NP) (both markers of bone formation) and N telopeptide (a marker of bone resorption) were measured as well. Osteocalcin and P1NP declined from baseline to month 6 and then stabilized, whereas N telopeptide reached its nadir within 1–2 months in the alendronate group. In the teriparatide group, all bone markers reached peak values 6 months after start of treatment, and then gradually declined. During the combined treatment, osteocalcin and P1NP rose steeply during the first 6 months and continued to increase throughout the study period, but the increase in N telopeptide was more gradual and more modest.


While monotherapy for osteoporosis is usually the current practice, studies on combination therapies have been performed too. The rationale for combining two medications is based on the fact that some patients do not gain enough from monotherapy and remain severely osteoporotic and exposed to significant risk of fractures. Prescribing two drugs, each having a different mode of action on bone metabolism, seems a logical and practical approach. Actually, all combinations have been tested: estrogen plus bisphosphonates and raloxifene with bisphosphonates showed more efficacy on BMD than hormone therapy alone [2-4]. The same result was found when teriparatide was added to hormone therapy [5]. The issue of PTH analogues and bisphosphonates may be more complex since there was some uncertainty about the sequence and timing of therapy: should one start with bisphosphonate monotherapy and then PTH monotherapy? Or vice versa, taking into account that the duration of PTH therapy is limited to 24 months? Should we wait for several months between these therapies? Is it worthwhile to initiate a combined therapy? Are all bisphosphonates similar in the case where patients are switched from a bisphosphonate to teriparatide? There is still much to learn, but the data so far indicate that prior therapy with a more potent antiresorptive agent may help to generate the higher anabolic effects of teriparatide. However, co-administration of a potent bisphosphonate with teriparatide may yield less satisfactory effects on BMD when compared to teriparatide monotherapy. The anti-fracture effect of such a combination is still unknown.


Amos Pines
Department of Medicine T, Ichilov Hospital, Tel-Aviv, Israel


  1. Finkelstein JS, Wyland JJ, Lee H, Neer RM. Effects of teriparatide, alendronate, or both in women with postmenopausal osteoporosis. J Clin Endocrinol Metab 2010; Feb 17. Epub ahead of print.

  2. Tseng LN, Sheu WH, Ho ES, et al. Effects of alendronate combined with hormone replacement therapy on osteoporotic postmenopausal Chinese women. Metabolism 2006;55:741-7.

  3. Johnell O, Scheele WH, Lu Y, et al. Additive effects of raloxifene and alendronate on bone density and biochemical markers of bone remodeling in postmenopausal women with osteoporosis. J Clin Endocrinol Metab 2002;87:985-92.

  4. Fadanelli ME, Bone HG. Combining bisphosphonates with hormone therapy for postmenopausal osteoporosis. Treat Endocrinol 2004;3:361-9.

  5. Ste-Marie LG, Schwartz SL, Hossain A, et al. Effect of teriparatide [rhPTH(1-34)] on BMD when given to postmenopausal women receiving hormone replacement therapy. J Bone Miner Res 2006;21:283-91.