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

Abstract

Whereas the beneficial effects of intermittent treatment with parathyroid hormone (PTH) (intact PTH 1-84 or fragment PTH 1-34, teriparatide) on vertebral strength is well documented, treatment may not be equally effective in the peripheral skeleton. We used highresolution peripheral quantitative computed tomography (HR-pQCT) to detail effects on compartmental geometry, density, and microarchitecture as well as finite element (FE) estimated integral strength at the distal radius and tibia in postmenopausal osteoporotic women treated with PTH 1-34 (20 mg sc daily, n ¼ 18) or PTH 1-84 (100 mg sc daily, n ¼ 20) for 18 months in an open-label, nonrandomized study. A group of postmenopausal osteoporotic women receiving zoledronic acid (5 mg infusion once yearly, n ¼ 33) was also included. Anabolic therapy increased cortical porosity in radius (PTH 1-34 32 AE 37%, PTH 1-84 39 AE 32%, both p < 0.001) and tibia (PTH 1-34 13 AE 27%, PTH 1-84 15 AE 22%, both p < 0.001) with corresponding declines in cortical density. With PTH 1-34, increases in cortical thickness in radius (2.0 AE 3.8%, p < 0.05) and tibia (3.8 AE 10.4%, p < 0.01) were found. Trabecular number increased in tibia with both PTH 1-34 (4.2 AE 7.1%, p < 0.05) and PTH 1-84 (5.3 AE 8.3%, p < 0.01). Zoledronic acid did not impact cortical porosity at either site but increased cortical thickness (3.0 AE 3.5%, p < 0.01), total (2.7 AE 2.5%, p < 0.001) and cortical density (1.5 AE 2.0%, p < 0.01) in tibia as well as trabecular volume fraction in radius (2.5 AE 5.1%, p < 0.05) and tibia (2.2 AE 2.2%, p < 0.01). FE estimated bone strength was preserved, but not increased, with PTH 1-34 and zoledronic acid at both sites, whereas it decreased with PTH 1-84 in radius (À2.8 AE 5.8%, p < 0.05) and tibia (-3.9 AE 4.8%, p < 0.001). Conclusively, divergent treatment-specific effects in cortical and trabecular bone were observed with anabolic and zoledronic acid therapy. The finding of decreased estimated strength with PTH 1-84 treatment was surprising and warrants confirmation. ß

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

“…25,[27][28][29] In that head-to-head study against zoledronate (above), 25 the percent change in Ct.Th measured at the end of the study was significantly higher for PTH 1-34 vs PTH 1-84 at both sites. Percent change in Ct.Th was significantly lower in the PTH 1-84 group compared with the ZOL group at the tibia.…”

“…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.…”

“…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. Hence the observed changes in microstructure have to be interpreted in light of parallel studies with fracture end points for a full understanding of their clinical significance.…”

“…25 HR-pQCT examinations of the distal radius (n ¼ 28) and distal tibia (n ¼ 30) were assessable. After 18 months, treatment with ZOL was associated with significant increases in BV/TV and Tb.N of both sites and significant increases in cortical thickness and density and in total density at the tibia with significant decreases in trabecular area and spacing also at the tibia.…”

Heterogeneidade na apresentação clínica de fraturas atípicas após uso prolongado de bisfosfonatos – Fatores de risco e marcadores de remodelação óssea

“…Hansen e cols. observaram aumento da porosidade cortical com uso de teriparatida, no entanto esse efeito foi contrabalanceado pelos efeitos benéficos na geometria do osso cortical e na massa do osso esponjoso (29). Assim, a teriparatida é uma droga promissora para o tratamento de FFA com baixa evidência de consolidação, particularmente após 4 a 6 semanas depois da intervenção cirúrgica (15).…”