Early effects of abaloparatide on bone formation and resorption indices in postmenopausal women with osteoporosis

Dempster, David W.; Zhou, Hua; Rao, Sudhaker D.; Recknor, Chris; Miller, Paul D.; Leder, Benjamin Z.; Annett, Miriam; Ominsky, Michael S.; Mitlak, Bruce H.

Affiliations

¹Regional Bone Center, Helen Hayes Hospital, West Haverstraw, NY, USA

²Bone & Mineral Research Laboratory, Henry Ford Health System, Detroit, MI, USA

³United Osteoporosis Centers, Gainesville, GA, USA

⁴Colorado Center for Bone Health, Lakewood, CO, USA

⁵Mass General Hospital, Harvard Medical School, Boston, MA, USA

⁶Radius Health, Inc., Boston, MA, USA

Abstract and keywords

Anabolic osteoporosis drugs improve bone mineral density by increasing bone formation. The objective of this study was to evaluate the early effects of abaloparatide on indices of bone formation and to assess the effect of abaloparatide on modeling‐based formation (MBF), remodeling‐based formation (RBF), and overflow MBF (oMBF) in transiliac bone biopsies. In this open‐label, single‐arm study, 23 postmenopausal women with osteoporosis were treated with 80 μg abaloparatide daily. Subjects received double fluorochrome labels before treatment and before biopsy collection at 3 months. Change in dynamic histomorphometry indices in four bone envelopes were assessed. Median mineralizing surface per unit of bone surface (MS/BS) increased to 24.7%, 48.7%, 21.4%, and 16.3% of total surface after 3 months of abaloparatide treatment, representing 5.5‐, 5.2‐, 2.8‐, and 12.9‐fold changes, on cancellous, endocortical, intracortical, and periosteal surfaces (p < .001 versus baseline for all). Mineral apposition rate (MAR) was significantly increased only on intracortical surfaces. Bone formation rate (BFR/BS) was significantly increased on all four bone envelopes. Significant increases versus baseline were observed in MBF on cancellous, endocortical, and periosteal surfaces, for oMBF on cancellous and endocortical surfaces, and for RBF on cancellous, endocortical, and intracortical surfaces. Overall, modeling‐based formation (MBF + oMBF) accounted for 37% and 23% of the increase in bone‐forming surface on the endocortical and cancellous surfaces, respectively. Changes from baseline in serum biomarkers of bone turnover at either month 1 or month 3 were generally good surrogates for changes in histomorphometric endpoints. In conclusion, treatment with abaloparatide for 3 months stimulated bone formation on cancellous, endocortical, intracortical, and periosteal envelopes in transiliac bone biopsies obtained from postmenopausal women with osteoporosis. These increases reflected stimulation of both remodeling‐ and modeling‐based bone formation, further elucidating the mechanisms by which abaloparatide improves bone mass and lowers fracture risk.

Keywords: ANABOLICS; BONE HISTOMORPHOMETRY; BONE MODELING AND REMODELING; CLINICAL TRIAL; OSTEOPOROSIS

Links

DOI: 10.1002/jbmr.4243

PubMed: 33434314

WoS: 000612489500001

History

Received: 2020-11-3

Revised: 2020-12-15

Accepted: 2021-01-3

Online: 2021-01-28

Cited Works (11)

Year	Entry
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Cited By (4)

Year	Entry
2022	Rooney AM, Dempster DW, Nieves JW, Zhou H, Bostrom MPG, Cosman F. Effects of teriparatide and loading modality on modeling-based and remodeling-based bone formation in the human femoral neck. Bone. April 2022;157:116342.
2022	Wang W, Azar T, Tseng W-J, Pei S, Zhou Y, Jiang X, Dyment N, Liu XS. Distinct responses of modeling- and remodeling-based bone formation to the discontinuation of intermittent parathyroid hormone treatment in ovariectomized rats. J Bone Miner Res. November 2022;37(11):2215-2225.
2023	Cosman F, Hans D, Shevroja E, Wang Y, Mitlak B. Effect of abaloparatide on bone microarchitecture assessed by trabecular bone score in women with osteoporosis: post hoc analysis of ACTIVE and ACTIVExtend. J Bone Miner Res. April 2023;38(4):464-470.
2022	van Dijk Christiansen P. The Relevance of Reversal Cells and Intermittent Parathyroid Hormone on the Duration of the Reversal-Resorption Phase in Intracortical Bone Remodeling Events [PhD thesis]. University of Southern Denmark (SDU); November 2022.