Anti-sclerostin antibodies and abaloparatide have additive effects when used as a countermeasure against disuse osteopenia in female rats

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Brent, Mikkel Bo^1,2; Brüel, Annemarie¹; Thomsen, Jesper Skovhus¹

Anti-sclerostin antibodies and abaloparatide have additive effects when used as a countermeasure against disuse osteopenia in female rats

Bone. July 2022;160:116417

©2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Affiliations

¹Department of Biomedicine, Aarhus University, Aarhus, Denmark

²Department of Orthopedic Surgery, Aalborg University Hospital, Aalborg, Denmark
Abstract and keywords

Prolonged disuse and substantial mechanical unloading are particularly damaging to skeletal integrity. Preclinical studies in rodents and clinical studies have highlighted the need for potent bone anabolic drugs to counteract disuse-induced osteopenia. The aim of present study was to compare the efficacy of romosozumab (Scl-Ab) and abaloparatide (ABL), alone or in combination, to prevent botulinum toxin (BTX) induced bone loss in a rat model. Eighty female Wistar rats were divided into the following six groups: 1. Baseline (n = 12); 2. Control (Ctrl) (n = 12); 3. BTX (n = 12); 4. BTX + Scl-Ab (n = 16); 5. BTX + ABL (n = 12); and 6. BTX + Scl-Ab + ABL (n = 16). Disuse was achieved by injecting 4 IU BTX into the hind limb musculature at study start. Scl-Ab (25 mg/kg) was injected s.c. twice weekly, while ABL (80 μg/kg) was injected s.c. five days a week for four weeks. Hind limb disuse dramatically decreased muscle mass and skeletal integrity and deteriorated the cortical morphology and trabecular microstructure. Treatment with Scl-Ab alone prevented most of the adverse cortical and trabecular effects of disuse, while ABL monotherapy mainly attenuated the disuse-induced loss of femoral areal bone mineral density (aBMD). Moreover, the combination of Scl-Ab and ABL not only counteracted most of the negative skeletal effects of unloading, but also increased aBMD (+10% and +20%), epiphyseal trabecular bone volume fraction (BV/TV) (+25% and +73%), and metaphyseal bone strength (+18% and +30%) significantly above that of Scl-Ab or ABL monotherapy, respectively. The potent and additive osteoanabolic effect of Scl-Ab and ABL, when given in combination, is highly intriguing and underlines that an osteoanabolic bone gain can be maximized by utilizing two pharmaceuticals targeting different cellular signaling pathways. From a clinical perspective, a combination treatment may be warranted in patients where the osteoanabolic effect of either monotherapy is not sufficient, or if a dose-reduction is required due to adverse effects.

Keywords: DXA; Osteoporosis; Bone loss; Abaloparatide; Romosozumab; Scl-Ab
Links

DOI: 10.1016/j.bone.2022.116417

PubMed: 35398589

WoS: 000791661600004
History

Received: 2022-02-24

Revised: 2022-04-1

Accepted: 2022-04-4

Online: 2022-04-7

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Cited By (1)

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2023	Li Z, Qiu K, Zhao J, Granger K, Yu H, Lewis AG, Myronovych A, Toure MH, Hatsell SJ, Economides AN, Seeley RJ, MacDougald OA. Antibodies to sclerostin or G-CSF receptor partially eliminate bone or marrow adipocyte loss, respectively, following vertical sleeve gastrectomy. Bone. April 2023;169:116682.