Differential Effects of Teriparatide on BMD After Treatment With Raloxifene or Alendronate

Abstract

We investigated the effects of 18 months of treatment with teriparatide in patients previously treated with long-term antiresorptive therapy using bone turnover markers and bone densitometry. Previous raloxifene treatment allowed for teriparatide-induced early bone marker and BMD increases comparable with previously published results for treatment-naïve patients. Conversely, previous alendronate treatment reduced the bone marker and BMD response.Introduction: ] has been shown to increase BMD and reduce the risk of fracture in postmenopausal women with osteoporosis. Our objective was to investigate the skeletal effects of 18 months of treatment with teriparatide in women whose osteoporosis was previously treated with either alendronate or raloxifene. Materials and Methods: Daily subcutaneous injections of 20 g teriparatide were administered for 18 months to 59 postmenopausal women, 60 -87 years of age, with BMD T-scores Յ Ϫ2.0 who had previously received either alendronate (ALN) or raloxifene (RLX) therapy for 18 -36 months. All patients received daily calcium (1000 mg) and vitamin D (400 IU) supplementation. The primary study outcome was change in lumbar spine BMD measured by DXA. Secondary outcomes included changes in bone turnover markers, total hip BMD, and safety. Results: Median baseline bone turnover marker levels in prior ALN patients were about one-half those of prior RLX patients. During teriparatide treatment, bone markers in prior ALN patients increased later and peaked at about one-third lower levels compared with prior RLX patients. During the first 6 months, there were statistically significant (p Ͻ 0.05) group differences in BMD change at the hip (prior ALN Ϫ1.8% versus prior RLX ϩ0.5%) and at the spine (prior ALN ϩ0.5% versus prior RLX ϩ5.2%). The positive slopes in hip and lumbar spine BMD were similar in both groups between 6 and 18 months. After 18 months, mean lumbar spine BMD increased 10.2% in prior RLX compared with 4.1% in prior ALN (p Ͻ 0.05) patients. Furthermore, at 18 months, mean total hip BMD had significantly increased (1.8%, p Ͻ 0.05) in prior RLX patients but was not different from baseline in prior ALN patients. Conclusions: Teriparatide treatment stimulates bone turnover in patients pretreated with both RLX and ALN. Prior treatment with RLX allows for the expected teriparatide-induced BMD increases comparable with those previously reported for treatment-naïve patients. In contrast, prior treatment with ALN prevents increases in BMD, particularly in the first 6 months.

Molecular and cellular mechanisms of the anabolic effect of intermittent PTH

“…RANKL may also stimulate the secretion of an osteoblastogenic factor from osteoclasts [106]. Evidence that bisphosphonates attenuated the anabolic effect of intermittent PTH in animal models and humans is consistent with the involvement of osteoclasts in the anabolic effect [107][108][109][110][111], but such inhibition was not seen in other studies [45,[112][113][114]. Indeed, both OPG and alendronate prolonged the duration of the anabolic effect in ovariectomized mice, apparently by preventing the increased bone resorption that occurs in the later stages of treatment [45].…”

Canadian Consensus Conference on Osteoporosis, 2006 Update

“…124 Estrogen and raloxifene do not appear to have the blunting effect on PTH therapy. [125][126][127][128] Fracture data are lacking and combination therapies are usually not recommended. Sequential therapies preceding or following PTH treatment are useful in maintaining and enhancing bone mass.…”

Effects of intravenous zoledronic acid plus subcutaneous teriparatide [rhPTH(1–34)] in postmenopausal osteoporosis

“…Prior studies evaluating combinations of PTH or teriparatide with antiresorptive agents have yielded inconsistent results, with differences related to which antiresorptive agent is used, (16)(17)(18)(19)(20)(21)(22) whether patients are treatment-naive or have been on antiresorptive therapy when combination treatment is started, (14,23) and, for patients on prior antiresorptives, whether the antiresorptive agent is continued or stopped when teriparatide is added. (24) In one study, (14) treatment-naive patients were randomized to alendronate or intact PTH(1-84) monotherapy versus combination therapy.…”