Microarchitectural deterioration of cortical and trabecular bone: Differing effects of denosumab and alendronate

Abstract

The intensity of bone remodeling is a critical determinant of the decay of cortical and trabecular microstructure after menopause. Denosumab suppresses remodeling more than alendronate, leading to greater gains in areal bone mineral density (aBMD). These greater gains may reflect differing effects of each drug on bone microarchitecture and strength. In a phase 2 double-blind pilot study, 247 postmenopausal women were randomized to denosumab (60mg subcutaneous 6 monthly), alendronate (70mg oral weekly), or placebo for 12 months. All received daily calcium and vitamin D. Morphologic changes were assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius and distal tibia and QCT at the distal radius. Denosumab decreased serum C-telopeptide more rapidly and markedly than alendronate. In the placebo arm, total, cortical, and trabecular BMD and cortical thickness decreased (−2.1% to −0.8%) at the distal radius after 12 months. Alendronate prevented the decline (−0.6% to 2.4%, p = .051 to < .001 versus placebo), whereas denosumab prevented the decline or improved these variables (0.3% to 3.4%, p < .001 versus placebo). Changes in total and cortical BMD were greater with denosumab than with alendronate (p ≤ .024). Similar changes in these parameters were observed at the tibia. The polar moment of inertia also increased more in the denosumab than alendronate or placebo groups (p < .001). Adverse events did not differ by group. These data suggest that structural decay owing to bone remodeling and progression of bone fragility may be prevented more effectively with denosumab.

Differing effects of PTH 1–34, PTH 1–84, and zoledronic acid on bone microarchitecture and estimated strength in postmenopausal women with osteoporosis: An 18-month open-labeled observational study using HR-pQCT

“…This is in accordance with previous findings on the effects of the bisphosphonates alendronate and ibandronate using HRpQCT. (26)(27)(28)(29) The response in the cancellous compartment with zoledronic acid in our study, with an increase in trabecular number in tibia, is in accordance with findings with alendronate in some (29) but not all studies. (27) Ibandronate did not exert significant effects on cancellous architecture compared with placebo after 2 years of treatment.…”

Osteoporosis drug effects on cortical and trabecular bone microstructure: a review of HR-pQCT analyses

“…Our search found 12 published articles describing the treatment-related effects on bone parameters assessed by HRpQCT imaging: Bisphosphonates (BPs) were tested in eight of these studies, [20][21][22][23][24][25][26][27] strontium ranelate (SR) in two, 22,23 denosumab (DMAB) in two, 21,27 teriparatide (TPTD) in four, 25,[28][29][30] PTH 1-84 in two 25,27 and odanacatib in one study, 31 sometimes in head-to-head comparisons, sometimes in combination. Most of these studies included postmenopausal women with some level of low BMD, with one exception concerning a TPTD study where premenopausal women with idiopathic osteoporosis were enrolled.…”

“…29 The number of patients and the design of these studies varied quite substantially ( Table 1). Some of these clinical trials were multicentric; [21][22][23][24]26,31 other studies were performed in a single center. 20,25,[27][28][29] None of these studies considered fracture incidence as an end point due to their relatively short duration and limited size.…”

Challenges in longitudinal measurements with HR-pQCT: Evaluation of a 3D registration method to improve bone microarchitecture and strength measurement reproducibility

“…Bone strength, estimated using micro-finite element analysis (μFEA), was also associated with prevalent fracture [6][7][8][9][10][11][12][13][14]. Moreover, HR-pQCT has been used to assess age-related bone loss [15][16][17][18][19] and to monitor variations in microarchitecture parameters during osteoporosis treatments [20][21][22][23][24][25][26].…”