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The Role of Osteogenic Effect and Vascular Function in Bone Health in Hypertensive Rats: A Study of Anti-hypertensive and Hemorheologic Drugs

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Abstract

Vascular dysfunction contributes to the development of osteopenia in hypertensive patients, as decreased blood supply to bones results in tissue damage and dysfunction. The effect of anti-hypertensive medicines on bone mass in hypertensive individuals is inconclusive because of the varied mechanism of their action, and suggests that reducing blood pressure (BP) alone is insufficient to enhance bone mass in hypertension. Pentoxifylline (PTX), a hemorheological drug, improves blood flow by reducing blood viscosity and angiogenesis, also has an osteogenic effect. We hypothesized that improving vascular function is critical to increasing bone mass in hypertension. To test this, we screened various anti-hypertensive drugs for their in vitro osteogenic effect, from which timolol and hydralazine were selected. In adult female spontaneously hypertensive rats (SHRs), timolol and hydralazine did not improve vascular function and bone mass, but PTX improved both. In female SHR animals, PTX restored bone mass, strength and mineralization, up to the level of normotensive control rats. In addition, we observed lower blood vasculature in the femur of adult SHR animals, and PTX restored them. PTX also restored the bone vascular and angiogenesis parameters that had been impaired in OVX SHR compared to sham SHR. This study demonstrates the importance of vascular function in addition to increased bone mass for improving bone health as achieved by PTX without affecting BP, and suggests a promising treatment option for osteoporosis in hypertensive patients, particularly at-risk postmenopausal women.

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Acknowledgements

Authors acknowledge the erudite suggestions of Prof. Asit R. Mridha, AIIMS, New Delhi for conducting histological assessments of bone samples.

Funding

Council of Scientific and Industrial Research (MLP 2035), Government of India to Naibedya Chattopadhyay. CDRI communication number for this article is 10703.

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Author notes

  1. Subhashis Pal and Shivani Sharma have equally contributed to this work.

Authors and Affiliations

  1. Division of Endocrinology, CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow, 226031, India

    Subhashis Pal, Shivani Sharma, Konica Porwal, Mahesh C. Tiwari, Yasir A. Khan & Naibedya Chattopadhyay

  2. Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India

    Shivani Sharma & Naibedya Chattopadhyay

  3. Department of Mechanical Engineering, Indian Institute of Technology Ropar, Rupnagar, 140001, Punjab, India

    Saroj Kumar & Navin Kumar

  4. Division of Endocrinology, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226 031, India

    Naibedya Chattopadhyay

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  1. Subhashis Pal
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Correspondence to Naibedya Chattopadhyay.

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Subhashis Pal, Shivani Sharma, Konica Porwal, Mahesh C. Tiwari, Yasir A. Khan, Saroj Kumar, Navin Kumar, Naibedya Chattopadhyay declare that they have no conflict of Interest.

Human and Animal Rights and Informed Consent statements

All animal experiments were performed following the ethical standards of The International Union for Conservation of Nature (IUCN) and approved by institutional committee for control and supervision of experiments on animals [The Institutional Animal Ethics Committee (IAEC) approval number for this study is CDRI/IAEC/2017/312)]. . The IAEC has been constituted by the Committee for the Control and Supervision of Experiments on Animals (CCSEA), the Government of India in which the Socially Aware Nominee of the CCSEA monitors all aspects of animal welfare and rights.

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Pal, S., Sharma, S., Porwal, K. et al. The Role of Osteogenic Effect and Vascular Function in Bone Health in Hypertensive Rats: A Study of Anti-hypertensive and Hemorheologic Drugs. Calcif Tissue Int 114, 295–309 (2024). https://doi.org/10.1007/s00223-023-01170-4

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