Abaloparatide treatment increases bone formation, bone density and bone strength without increasing bone resorption in a rat model of hindlimb unloading

Teguh, Dian; Nustad, Jordan L.; Craven, Amanda; Brooks, Daniel J.; Arlt, Heike; Hu, Dorothy; Baron, Roland; Lanske, Beate; Bouxsein, Mary L.

doi:10.1016/j.bone.2020.115801

Cited by 10 publications

(10 citation statements)

References 46 publications

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“…76 The findings are also in disagreement with recent reports showing protection by abaloparatide of bone loss after hindlimb unloading or botulinum toxin-induced paralysis in young adult male and female rats, respectively. [73][74][75] These differences can be ascribed to the severity and complexity of bone damage after complete paraplegia with spinal cord injury. Factors that could attenuate the response of the sub-lesional skeleton to abaloparatide in F I G U R E 8 Effects of abaloparatide treatment (80 μg/kg/day) on femoral BM levels of bone turnover markers and RANKL and OPG: Female C57BL/6J sham and SCI mice were injected daily except Sunday with either vehicle or 80 μg/kg/day abaloparatide.…”

Section: Discussionmentioning

confidence: 99%

“…63 Recently, abaloparatide was shown to protect against bone loss in rat models of mechanical unloading. [73][74][75] Whether abaloparatide treatment will protect against disuse-induced bone loss after SCI remains undetermined. Thus, this study determined the efficacy of abaloparatide to prevent immobilization-induced bone loss in a mouse model of paraplegia after severe contusion SCI.…”

Section: Introductionmentioning

confidence: 99%

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Abaloparatide prevents immobilization‐induced cortical but not trabecular bone loss after spinal cord injury

et al. 2023

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Spinal cord injury (SCI) causes severe and resistant sublesional disuse bone loss.Abaloparatide, a modified parathyroid hormone related peptide, is an FDA approved drug for treatment of severe osteoporosis with potent anabolic activity.The effects of abaloparatide on SCI-induced bone loss remain undefined. Thus, female mice underwent sham or severe contusion thoracic SCI causing hindlimb paralysis. Mice then received subcutaneous injection of vehicle or 20 μg/kg/day abaloparatide for 35 days. Micro-computed tomography (micro-CT) analysis of the distal and midshaft femoral regions of the SCI-vehicle mice revealed reduced trabecular fractional bone volume (56%), thickness (75%), and cortical thickness (80%) compared to sham-vehicle controls. Treatment with abaloparatide did not prevent SCI-induced changes in trabecular or cortical bone. However, histomorphometry evaluation of the SCI-abaloparatide mice demonstrated that abaloparatide treatment increased osteoblast (241%) and osteoclast (247%) numbers and the mineral apposition rate (131%) compared to SCI-vehicle animals. In another independent experiment, treatment with 80 μg/kg/day abaloparatide significantly attenuated SCI-induced loss in cortical bone thickness (93%) when compared to SCI-vehicle mice (79%) but did not prevent SCI-induced trabecular bone loss or elevation in cortical porosity. Biochemical analysis of the bone marrow supernatants of the femurs showed that SCI-abaloparatide animals had 2.3-fold increase in procollagen type I N-terminal propeptide, a bone formation marker than SCIvehicle animals. SCI groups had 70% higher levels of cross-linked C-telopeptide of type I collagen, a bone resorption marker, than sham-vehicle mice. These findings suggest that abaloparatide protects the cortical bone against the deleterious effects of SCI by promoting bone formation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Abaloparatide prevents immobilization‐induced cortical but not trabecular bone loss after spinal cord injury

et al. 2023

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“…3,18 ABL (25 mg/kg) was injected subcutaneously daily. 44,47 Saline was injected into the CON group subcutaneously daily as a control. All rats could perform cage activities without immobilization.…”

Section: Surgical Techniquesmentioning

confidence: 99%

“…At 4 and 8 weeks, the ratio of bone volume to total volume in the ABL group was significantly higher than that in the CON group (29. 44…”

Section: Micro-ct Analysismentioning

confidence: 99%

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Abaloparatide Improves Rotator Cuff Healing via Anabolic Effects on Bone Remodeling in a Chronic Rotator Cuff Tear Model of Rat With Osteoporosis: A Comparison With Denosumab

Chen

et al. 2022

Am J Sports Med

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Background: Because of poor clinical outcomes, rotator cuff healing in patients with osteoporosis has recently gained attention. Antiresorptive therapy for osteoporosis has been reported to improve healing after repair. However, the comparative effectiveness of anabolic and antiresorptive agents has not been investigated. Hypothesis: Anabolic therapy with abaloparatide (ABL) would outperform antiresorptive therapy with denosumab (Dmab) to improve rotator cuff healing in the osteoporotic status. Study Design: Controlled laboratory study. Methods: A chronic rotator cuff tear model was established in ovariectomy-induced postmenopausal osteoporotic rats. Then, bilateral rotator cuff repairs were conducted in all experimental rats, which were randomly divided into control (CON), Dmab, and ABL groups to receive the corresponding subcutaneous injections. The rats sacrificed at 2 weeks (the early healing period) were used to detect osteoblast and osteoclast activities, related gene expression (osteoclastogenesis, osteogenesis, and chondrogenesis), new bone formation, and mineralization. In the rats sacrificed at 4 and 8 weeks, the bone mineral density and bone architecture at the repaired site were assessed by micro–computed tomography, and rotator cuff healing was evaluated using histological and biomechanical analyses. Results: At 8 weeks, significantly higher failure load and stiffness were observed in the ABL (25.13 ± 3.54 N, P < .001; 21.65 ± 3.08 N/mm, P < .001; respectively), and Dmab (21.21 ± 2.55 N, P < .001; 16.15 ± 2.07 N/mm, P = .008; respectively) groups than in the CON group (13.36 ± 1.70 N; 11.20 ± 2.59 N/mm; respectively), whereas the ABL treatment provided better failure load and stiffness than Dmab ( P = .019; P = .003). Although tendon-to-bone healing was improved by Dmab, the most mature tendon insertion at the interface was observed in the ABL group, including a more organized collagen and fibrocartilage and higher bone quality. ABL significantly promoted bone remodeling via coupling between osteoclasts and osteoblasts (osteoblast to osteoclast ratio: 4.80 ± 0.39; P = .022), thereby stimulating more new bone formation and mineralization at the tendon-to-bone healing interface than Dmab (osteoblast to osteoclast ratio: 3.21 ± 0.75) at 2 weeks. Moreover, ABL had significant effects on gene expression [Runt-realted transcription factor 2 ( Runx2, collagen type I-alpha 1 ( Col1A1]), and sclerostin for osteogenesis; aggrecan and collagen type II ( Col2) for chondrogenesis] in mineralized tissues, indicative of enhanced bone and fibrocartilage formation when compared with the CON and Dmab groups. Conclusion: ABL promoted rotator cuff healing in osteoporotic rats by significantly increasing the mineralized tissue quality and collagen maturity at the reattachment site, leading to improved biomechanical properties, and was superior to Dmab in both biomechanical and histological analyses. Clinical Relevance: Anabolic therapy with ABL may outperform antiresorptive therapy with Dmab in improving outcomes after rotator cuff repair in osteoporotic patients.

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

Brent

Brüel

Thomsen

2022

Bone

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Abaloparatide treatment increases bone formation, bone density and bone strength without increasing bone resorption in a rat model of hindlimb unloading

Cited by 10 publications

References 46 publications

Abaloparatide prevents immobilization‐induced cortical but not trabecular bone loss after spinal cord injury

Abaloparatide prevents immobilization‐induced cortical but not trabecular bone loss after spinal cord injury

Abaloparatide Improves Rotator Cuff Healing via Anabolic Effects on Bone Remodeling in a Chronic Rotator Cuff Tear Model of Rat With Osteoporosis: A Comparison With Denosumab

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

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