Antiresorptives overlapping ongoing teriparatide treatment result in additional increases in bone mineral density

Abstract

During teriparatide (TPTD) treatment, high levels of bone formation are accompanied by an increase in bone resorption. The aim of this work was to test if coadministration of raloxifene (RAL) or alendronate (ALN) following 9 months of ongoing TPTD therapy would reopen the anabolic window, thereby exerting additional benefit on bone mineral density (BMD). Postmenopausal women (n ¼ 125) with severe osteoporosis on TPTD treatment for 9 months were randomized into three open-label groups for a further 9 months: ALN (70 mg/week) in addition to TPTD; RAL (60 mg/d) in addition to TPTD; or no medication in addition to TPTD. Amino-terminal propeptide of type I procollagen (P1NP) and cross-linked C-telopeptide (CTX), and areal and volumetric BMD at the lumbar spine and hip were assessed. During the combination period, P1NP concentrations did not change on TPTD monotherapy (693% AE 371%, p < 0.0001) and decreased in the ALN (360% AE 153%, p < 0.0001) and RAL (482% AE 243%, p < 0.0001) combination groups; whereas CTX did not change on TPTD monotherapy (283% AE 215%, p < 0.0001), decreased to the starting level in the ALN combination group (17% AE 72%, p ¼ 0.39), and remained elevated in the RAL combination group (179% AE 341%, p < 0.0001). The increase in lumbar spine BMD was 5% AE 6.3% in the ALN and 6% AE 5.2% in the RAL combination groups compared with 2.8% AE 9.3% in the TPTD monotherapy group (p ¼ 0.085 and p ¼ 0.033, respectively). The increase of trabecular lumbar spine BMD for both the ALN and RAL combination groups was superior to TPTD monotherapy. Total hip BMD changes were 4% AE 5.3% for the ALN combination group and 1.4% AE 5.1% for the TPTD monotherapy (p ¼ 0.032), and 1.4% AE 3.4% (p ¼ 0.02) for the RAL combination group. With the exception of no differences in the trabecular compartment of femoral neck, volumetric BMD changes in the ALN combination group for all other comparisons were significantly superior to the two other groups. Our data suggest that ALN when added to TPTD 9 months after initiation of TPTD monotherapy results in a more robust increase in BMD, probably due to a reopening of the anabolic window. The clinical relevance of the BMD increase is unknown. ß

Teriparatide increases the insertional torque of pedicle screws during fusion surgery in patients with postmenopausal osteoporosis

“…6,8,31,32 Treatment using teriparatide is associated with a significant increase of bone mass in the lumbar spine. 14,26,28,44 We previously reported that teriparatide administered daily for 2 months before surgery reduced the incidence of pedicle screw loosening after instrumented lumbar fusion in postmenopausal women with osteoporosis, suggesting that teriparatide increased not only bone mass, but also the quality of the pedicle cortex. 34 However, a clinical study of the effect of teriparatide on pedicle screw insertional torque in postmenopausal women with osteoporosis has not yet been reported.…”

Enhanced Individual Trabecular Repair and Its Mechanical Implications in Parathyroid Hormone and Alendronate Treated Rat Tibial Bone

“…While these young, healthy ALN-treated rats did not display any reduction in connectivity deterioration compared to Veh, the addition of ALN to PTH resulted in a significant reduction in connectivity deterioration of both rod and plate trabeculae. The additive effect of combined PTH and anticatabolic therapy is supported by a growing body of existing literature [10,15,16,[45][46][47][48][49]. Our previous work showed that increased trabecular thickening was similar in both PTH and PTHþALN groups, and suggested the additive effect may be related to the higher occurrence of plate-like trabeculae [17].…”

“…Combined therapies of antiresorptive treatments and PTH have been proposed and are expected to further increase bone mass. Despite conflicting results in both clinical and preclinical studies [8][9][10][11][12][13][14][15][16], previous work in our lab has shown that combined therapy of PTH and alendronate (ALN), a bisphosphonate, results in an additive effect on bone volume fraction in intact 1 female rats [17]. While combined treatment and PTH monotreatment had a similar effect on stimulating new bone formation and improving trabecular thickness (Tb.Th), the addition of ALN to PTH further improves the relative bone volume and number of plate-versus rod-like structures [17].…”

“…While the effect of the current available osteoporosis drug treatments on bone structure, mechanical properties, and fracture risk reduction have been extensively studied [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17], there is limited data on their ability to enhance connectivity repair to restore lost mechanical function. This critical knowledge gap is partly due to the technical challenge of in vivo tracking of bone connectivity changes at an individual trabecula level.…”

Is there a role for combination therapy for osteoporosis?

“…Muschitz et al [13] investigated women treated with teriparatide for 9 months and then randomized to remain on teriparatide alone or add alendronate or raloxifene plus ongoing teriparatide for an additional 9 months. The BMD gains at the end of the study were significantly greater in both spine and total hip in the teriparatide/alendronate combination group compared to teriparatide alone.…”