Hip and spine strength effects of adding versus switching to teriparatide in postmenopausal women with osteoporosis treated with prior alendronate or raloxifene

Abstract

Many postmenopausal women treated with teriparatide for osteoporosis have previously received antiresorptive therapy. In women treated with alendronate (ALN) or raloxifene (RLX), adding versus switching to teriparatide produced different responses in areal bone mineral density (aBMD) and biochemistry; the effects of these approaches on volumetric BMD (vBMD) and bone strength are unknown. In this study, postmenopausal women with osteoporosis receiving ALN 70 mg/week (n ¼ 91) or RLX 60 mg/day (n ¼ 77) for !18 months were randomly assigned to add or switch to teriparatide 20 mg/day. Quantitative computed tomography scans were performed at baseline, 6 months, and 18 months to assess changes in vBMD; strength was estimated by nonlinear finite element analysis. A statistical plan specifying analyses was approved before assessments were completed. At the spine, median vBMD and strength increased from baseline in all groups (13.2% to 17.5%, p < 0.01); there were no significant differences between the Add and Switch groups. In the RLX stratum, hip vBMD and strength increased at 6 and 18 months in the Add group but only at 18 months in the Switch group (Strength, Month 18: 2.7% Add group, p < 0.01 and 3.4% Switch group, p < 0.05). In the ALN stratum, hip vBMD increased in the Add but not in the Switch group (0.9% versus -0.5% at 6 months and 2.2% versus 0.0% at 18 months, both p 0.004 group difference). At 18 months, hip strength increased in the Add group (2.7%, p < 0.01) but not in the Switch group (0%); however, the difference between groups was not significant (p ¼ 0.076). Adding or switching to teriparatide conferred similar benefits on spine strength in postmenopausal women with osteoporosis pretreated with ALN or RLX. Increases in hip strength were more variable. In RLX-treated women, strength increased more quickly in the Add group; in ALN-treated women, a significant increase in strength compared with baseline was seen only in the Add group. ß

Treatment Sequence Matters: Anabolic and Antiresorptive Therapy for Osteoporosis

“…In the spine, effects of TPTD after bisphosphonates and denosumab remain positive, although slightly blunted. (24)(25)(26)(27)(28)(30)(31)(32)(33)(34) Furthermore, even after transition from denosumab to TPTD, the resultant spine BMD level was the same 2 years after the transition as it was when the sequence began with TPTD followed by denosumab. (28) The findings are very different for the hip region, as we describe below.…”

“…(18)(19)(20)(21)(22)(23) This is certainly true of TPTD and PTH. (24)(25)(26)(27)(28)(29)(30) BMD responses to initial TPTD/PTH followed by potent antiresorptive therapy are substantial in both spine and hip sites as a result of the effects of both components of the treatment sequence. (28,(31)(32)(33)(34) In contrast, several studies have indicated that hip BMD responses to TPTD are lower in patients who have already been pretreated with potent antiresorptive therapies and consistently decline transiently for the first year or even longer.…”

“…(28,(31)(32)(33)(34) In contrast, several studies have indicated that hip BMD responses to TPTD are lower in patients who have already been pretreated with potent antiresorptive therapies and consistently decline transiently for the first year or even longer. (24)(25)(26)(27)(28)30) Although there are no fracture endpoint trials in these antiresorptive pretreated patients, the substantial differences in BMD outcome, particularly for the hip region, suggest that TPTD effects against fracture could also differ in these pretreated patients. More than 50% of TPTD prescriptions are written for this group of patients, (35) so these observations have important clinical significance.…”

Goal-Directed Treatment for Osteoporosis: A Progress Report From the ASBMR-NOF Working Group on Goal-Directed Treatment for Osteoporosis

“…(38) It is not clear that switching treatment will offer additional reduction in risk of nonvertebral fracture. (4,(39)(40)(41)(42)(43)(44) Based on studies from patients who are not receiving treatment, the increase in risk of fracture associated with an incident nonvertebral fracture may be greatest in the first 5 years after the fracture occurs and then wane with time. (24)(25)(26)(27)(28)(29)(30)(31) Furthermore, in patients receiving zoledronic acid, incident nonvertebral fracture is an important risk factor for future nonvertebral fractures over the next 3 years if therapy is discontinued.…”

“…(4,(39)(40)(41)(42)(43)(44) The Working Group recommends that trials be conducted comparing continuing bisphosphonate therapy versus switching to presumably more potent treatments for patients who have not reached a goal, or who continue to have high fracture risk. These trials should continue for at least 3 years to provide data about the probability that switching treatment will achieve a T-score goal with longer therapy.…”