Skip to main content
Top
Published in: BMC Musculoskeletal Disorders 1/2022

Open Access 01-12-2022 | Verapamil | Research

Effect of verapamil on bone mass, microstructure and mechanical properties in type 2 diabetes mellitus rats

Authors: Xiaodan Wu, He Gong, Xiaorong Hu, Peipei Shi, Haipeng Cen, Chenchen Li

Published in: BMC Musculoskeletal Disorders | Issue 1/2022

Login to get access

Abstract

Background

Verapamil was mainly used to treat hypertension, cardiovascular disease, inflammation and improve blood glucose in patients with diabetes, but its effects on bone mass, microstructure and mechanical properties were unclear. This study described the effects of verapamil on bone mass, microstructure, macro and nano mechanical properties in type 2 diabetic rats.

Methods

Rat models of type 2 diabetes were treated with verapamil at doses of 4, 12, 24 and 48 mg/kg/day by gavage respectively, twice a day. After 12 weeks, all rats were sacrificed under general anesthesia. Blood glucose, blood lipid, renal function and biochemical markers of bone metabolism were obtained by serum analysis, Micro-CT scanning was used to assess the microstructure parameters of cancellous bone of femoral head, three-point bending test was used to measure maximum load and elastic modulus of femoral shaft, and nano-indentation tests were used to measure indentation moduli and hardnesses of longitudinal cortical bone in femoral shaft, longitudinal and transverse cancellous bones in femoral head.

Results

Compared with T2DM group, transverse indentation moduli of cancellous bones in VER 24 group, longitudinal and transverse indentation moduli and hardnesses of cancellous bones in VER 48 group were significantly increased (p < 0.05). Furthermore, the effects of verapamil on blood glucoses, microstructures and mechanical properties in type 2 diabetic rats were dependent on drug dose. Starting from verapamil dose of 12 mg/kg/day, with dose increasing, the concentrations of P1NP, BMD, BV/TV, Tb. Th, Tb. N, maximum loads, elastic moduli, indentation moduli and hardnesses of femurs in rats in treatment group increased gradually, the concentrations of CTX-1 decreased gradually, but these parameters did not return to the level of the corresponding parameters of normal rats. Verapamil (48 mg/kg/day) had the best therapeutic effect.

Conclusion

Verapamil treatment (24, 48 mg/kg/day) significantly affected nano mechanical properties of the femurs, and tended to improve bone microstructures and macro mechanical properties of the femurs, which provided guidance for the selection of verapamil dose in the treatment of type 2 diabetic patients.
Literature
14.
go back to reference Suzuki K, Kurose T, Takizawa M, Maruyamaa M, Ushikawaa K, Kikuyamac M, et al. Osteoclastic function is accelerated in male patients with type 2 diabetes mellitus: the preventive role of osteoclastogenesis inhibitory factor/osteoprotegerin (OCIF/OPG) on the decrease of bone mineral density. Diabetes Res Clin Pract. 2005;68(2):117–25. https://doi.org/10.1016/j.diabres.2004.08.006.CrossRefPubMed Suzuki K, Kurose T, Takizawa M, Maruyamaa M, Ushikawaa K, Kikuyamac M, et al. Osteoclastic function is accelerated in male patients with type 2 diabetes mellitus: the preventive role of osteoclastogenesis inhibitory factor/osteoprotegerin (OCIF/OPG) on the decrease of bone mineral density. Diabetes Res Clin Pract. 2005;68(2):117–25. https://​doi.​org/​10.​1016/​j.​diabres.​2004.​08.​006.CrossRefPubMed
18.
21.
go back to reference Atalar E, Eskin F, Tugtekin HB, Karabulut A, Kanyilmaz S, Kirbiyik H, et al. A prospective noninterventional, observational study to describe the effectiveness and safety of trandolapril and verapamil single-pill combination in the management of patients with hypertension and type 2 diabetes mellitus: a harvest TR study. Biomed Res Int. 2020;1-7. https://doi.org/10.1155/2020/2123601. Atalar E, Eskin F, Tugtekin HB, Karabulut A, Kanyilmaz S, Kirbiyik H, et al. A prospective noninterventional, observational study to describe the effectiveness and safety of trandolapril and verapamil single-pill combination in the management of patients with hypertension and type 2 diabetes mellitus: a harvest TR study. Biomed Res Int. 2020;1-7. https://​doi.​org/​10.​1155/​2020/​2123601.
37.
go back to reference Wood AC, Jensen ET, Bertoni AG, Ramesh G, Rich SS, Rotter JI, et al. Defining the relative role of insulin clearance in early dysglycemia in relation to insulin sensitivity and insulin secretion: the microbiome and insulin longitudinal evaluation study (MILES). Metabolites. 2021;11(7):1–15. https://doi.org/10.3390/metabo11070420.CrossRef Wood AC, Jensen ET, Bertoni AG, Ramesh G, Rich SS, Rotter JI, et al. Defining the relative role of insulin clearance in early dysglycemia in relation to insulin sensitivity and insulin secretion: the microbiome and insulin longitudinal evaluation study (MILES). Metabolites. 2021;11(7):1–15. https://​doi.​org/​10.​3390/​metabo11070420.CrossRef
56.
Metadata
Title
Effect of verapamil on bone mass, microstructure and mechanical properties in type 2 diabetes mellitus rats
Authors
Xiaodan Wu
He Gong
Xiaorong Hu
Peipei Shi
Haipeng Cen
Chenchen Li
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2022
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/s12891-022-05294-w

Other articles of this Issue 1/2022

BMC Musculoskeletal Disorders 1/2022 Go to the issue