Is combination therapy with parathyroid hormone (PTH) and bisphosphonate effective in the treatment of osteoporosis?

Updated: Jan 20, 2021
  • Author: Rachel Elizabeth Whitaker Elam, MD, MSc; Chief Editor: Herbert S Diamond, MD  more...
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Answer

According to Finkelstein et al, initial studies using a combination of concurrent PTH and bisphosphonate therapy showed decreased benefit compared with therapy with either agent alone; therefore, the general recommendation is that these drugs be given separately and in sequence. [178]

A study by Cosman and colleagues challenged this conclusion by giving 3-month-on, 3-month-off pulses of teriparatide while the patients were on weekly alendronate; BMD in the spine increased above that of the alendronate-only arm. [179] This pulsed regimen appears to take advantage of the 3- to 4-month so-called anabolic window, in which the markers of bone formation rise more quickly than the markers of bone resorption.

Studies in women by Deal et al and Ste-Marie et al have shown that the concurrent use of estrogen or raloxifene can enhance the bone-forming effects of teriparatide. [180, 181] Data on the use of PTH in men are much more limited, but its efficacy appears to be relatively comparable.

In a randomized, controlled trial (DATA), 94 osteoporotic postmenopausal women were randomized to take 24 months of teriparatide or denosumab alone, or teriparatide and denosumab in combination. Those women taking teriparatide and denosumab in combination had increased BMD after 12 months. The 12-month changes in posterior-anterior lumbar spine, femoral neck, and total hip BMD in the combination-therapy group (9.1%, 4.2% and 4.9%, respectively) were greater than those in the groups receiving only teriparatide (6.2%, 0.8% and 0.7%, respectively) or only denosumab (5.5%, 2.1% and 2.5%, respectively). [182]  

As an extension to this study (DATA-Switch), women originally assigned to teriparatide received denosumab after 24 months and those originally assigned to denosumab received teriparatide. Switching from teriparatide to denosumab yielded progressive BMD increases, whereas switching from denosumab to teriparatide resulted in progressive or transient bone loss. [183]  Given those findings, using teriparatide early in the treatment course before instituting other therapies when severe osteoporosis is diagnosed is preferred.

In a retrospective analysis of the data from the Fracture Prevention Trial and the Multiple Outcomes of Raloxifene Evaluation trial, Bouxsein et al found that teriparatide reduced fracture risk to a greater extent than raloxifene in postmenopausal osteoporotic women. Compared with placebo, teriparatide reduced the risk of any new fractures by 72%, new adjacent fractures by 75%, and new nonadjacent vertebral fractures by 70%. Raloxifene reduced the risks by 54%, 54%, and 53%, respectively. [184]

A double-blind, double-dummy trial by Kendler et al found that in postmenopausal women with severe osteoporosis, the risk of new vertebral and clinical fractures was significantly lower in patients receiving teriparatide than in those receiving risedronate. Study subjects had experienced at least two moderate or one severe vertebral fracture and had a BMD T-score of -1.50 or less. They were randomly assigned to receive teriparatide (daily injections of 20 μg) plus oral weekly placebo or risedronate (35 mg orally once weekly) plus daily injections of placebo for 24 months. [185]

At 24 months, new vertebral fractures had occurred in 28 (5.4%) of 680 patients in the teriparatide group and 64 (12.0%) of 680 patients in the risedronate group (hazard ratio [HR] 0.44, 95% confidence index [CI] 0.29-0.68; P < 0·0001). Clinical fractures occurred in 30 (4.8%) of 680 patients in the teriparatide group compared with 61 (9.8%) of 680 in the risedronate group (hazard ratio 0.48, 95% CI 0.32-0.74; P=0.0009). [185]


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