Strontium ranelate retards disc degradation and improves endplate and bone micro-architecture in ovariectomized rats with lumbar fusion induced – Adjacent segment disc degeneration

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Abstract

Objectives

Adjacent segment disc degeneration (ASDD) is one of the long-term sequelae of spinal fusion, which is more susceptible with osteoporosis. As an anti-osteoporosis drug, strontium ranelate (SR) has been reported to not only regulate bone metabolism but also cartilage matrix formation. However, it is not yet clear whether SR has a reversal or delaying effect on fusion-induced ASDD in a model of osteoporosis.

Materials and methods

Fifth three-month-old female Sprague-Dawley rats that underwent L4-L5 posterolateral lumbar fusion (PLF) with spinous-process wire fixation 4 weeks after bilateral ovariectomy (OVX) surgery. Animals were administered vehicle (V) or SR (900 mg/kg/d) orally for 12 weeks post-PLF as follows: Sham+V, OVX + V, PLF + V, OVX + PLF + V, and OVX + PLF + SR. Manual palpation and X-ray were used to evaluate the state of lumbar fusion. Adjacent-segment disc was assessed by histological (VG staining and Scoring), histomorphometry (Disc Height, MVD, Calcification rate and Vascular Bud rate), immunohistochemical (Col-II, Aggrecan, MMP-13, ADAMTS-4 and Caspase-3), and mRNA analysis (Col—I, Col-II, Aggrecan, MMP-13 and ADAMTS-4). Adjacent L6 vertebrae microstructures were evaluated by microcomputed tomography.

Results

Manual palpation and radiographs showed clear evidence of the fused segment's immobility. After 12 weeks of PLF surgery, a fusion-induced ASDD model was established. Low bone mass caused by ovariectomy can significantly exacerbate ASDD progression. SR exerted a protective effect on adjacent segment intervertebral disc with the underlying mechanism possibly being associated with preserving bone mass to prevent spinal instability, maintaining the functional integrity of endplate vascular microstructure, and regulating matrix metabolism in the nucleus pulposus and annulus fibrosus.

Discussion

Anti-osteoporosis medication SR treatments not only maintain bone mass and prevent fractures, but early intervention could also potentially delay degenerative conditions linked to osteoporosis. Taken together, our results suggested that SR might be a promising approach for the intervention of fusion-induced ASDD with osteoporosis.

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Most cited references 48

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Osteoporosis

Juliet Compston, Michael McClung, William D Leslie (2019)

Fractures resulting from osteoporosis become increasingly common in women after age 55 years and men after age 65 years, resulting in substantial bone-associated morbidities, and increased mortality and health-care costs. Research advances have led to a more accurate assessment of fracture risk and have increased the range of therapeutic options available to prevent fractures. Fracture risk algorithms that combine clinical risk factors and bone mineral density are now widely used in clinical practice to target high-risk individuals for treatment. The discovery of key pathways regulating bone resorption and formation has identified new approaches to treatment with distinctive mechanisms of action. Osteoporosis is a chronic condition and long-term, sometimes lifelong, management is required. In individuals at high risk of fracture, the benefit versus risk profile is likely to be favourable for up to 10 years of treatment with bisphosphonates or denosumab. In people at a very high or imminent risk of fracture, therapy with teriparatide or abaloparatide should be considered; however, since treatment duration with these drugs is restricted to 18-24 months, treatment should be continued with an antiresorptive drug. Individuals at high risk of fractures do not receive adequate treatment and strategies to address this treatment gap-eg, widespread implementation of Fracture Liaison Services and improvement of adherence to therapy-are important challenges for the future.

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Small molecule-based treatment approaches for intervertebral disc degeneration: Current options and future directions

Amir Kamali, Reihane Ziadlou, Gernot Lang … (2021)

Low back pain (LBP) is a major reason for disability, and symptomatic intervertebral disc (IVD) degeneration (IDD) contributes to roughly 40% of all LBP cases. Current treatment modalities for IDD include conservative and surgical strategies. Unfortunately, there is a significant number of patients in which conventional therapies fail with the result that these patients remain suffering from chronic pain and disability. Furthermore, none of the current therapies successfully address the underlying biological problem - the symptomatic degenerated disc. Both spinal fusion as well as total disc replacement devices reduce spinal motion and are associated with adjacent segment disease. Thus, there is an unmet need for novel and stage-adjusted therapies to combat IDD. Several new treatment options aiming to regenerate the IVD are currently under investigation. The most common approaches include tissue engineering, growth factor therapy, gene therapy, and cell-based treatments according to the stage of degeneration. Recently, the regenerative activity of small molecules (low molecular weight organic compounds with less than 900 daltons) on IDD was demonstrated. However, small molecule-based therapy in IDD is still in its infancy due to limited knowledge about the mechanisms that control different cell signaling pathways of IVD homeostasis. Small molecules can act as anti-inflammatory, anti-apoptotic, anti-oxidative, and anabolic agents, which can prevent further degeneration of disc cells and enhance their regeneration. This review pursues to give a comprehensive overview of small molecules, focusing on low molecular weight organic compounds, and their potential utilization in patients with IDD based on recent in vitro, in vivo, and pre-clinical studies.

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Age-Related Changes in Trabecular and Cortical Bone Microstructure

Huayue Chen, Xiangrong Zhou, Hiroshi Fujita … (2013)

The elderly population has substantially increased worldwide. Aging is a complex process, and the effects of aging are myriad and insidious, leading to progressive deterioration of various organs, including the skeleton. Age-related bone loss and resultant osteoporosis in the elderly population increase the risk for fractures and morbidity. Osteoporosis is one of the most common conditions associated with aging, and age is an independent risk factor for osteoporotic fractures. With the development of noninvasive imaging techniques such as computed tomography (CT), micro-CT, and high resolution peripheral quantitative CT (HR-pQCT), imaging of the bone architecture provides important information about age-related changes in bone microstructure and estimates of bone strength. In the past two decades, studies of human specimens using imaging techniques have revealed decreased bone strength in older adults compared with younger adults. The present paper addresses recently studied age-related changes in trabecular and cortical bone microstructure based primarily on HR-pQCT and micro-CT. We specifically focus on the three-dimensional microstructure of the vertebrae, femoral neck, and distal radius, which are common osteoporotic fracture sites.

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Author and article information

Contributors

Zhuang Zhou

Journal

Journal ID (nlm-ta): Bone Rep

Journal ID (iso-abbrev): Bone Rep

Title: Bone Reports

Publisher: Elsevier

ISSN (Electronic): 2352-1872

Publication date PMC-release: 15 February 2024

Publication date Collection: March 2024

Publication date (Electronic): 15 February 2024

Volume: 20

Electronic Location Identifier: 101744

Affiliations

[a ]Department of Orthopedic Surgery, The First Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China

[b ]Medical Research Center, North China University of Science and Technology, Tangshan, People's Republic of China

[c ]Department of Orthopedic Surgery, The Affiliated Hospital of North China University of Science and Technology, Tangshan, People's Republic of China

[d ]Department of Musculoskeletal Oncology, The Third Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China

[e ]Department of Orthopedic Surgery, Emergency General Hospital, Beijing, People's Republic of China

[f ]Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China

[g ]Department of Orthopedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China

[h ]Department of Radiology, the Third Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China

Author notes

[* ]Corresponding author at: Department of Musculoskeletal Oncology, The Third Hospital of Hebei Medical University, 361 Zhongshan E Rd, Shijiazhuang, Hebei 063000, China. 38500453@ 123456hebmu.edu.cn

Article

Publisher Item ID: S2352-1872(24)00011-1 Publisher ID: 101744

DOI: 10.1016/j.bonr.2024.101744

PMC ID: 10884424

SO-VID: d88fde88-7dfd-4263-8495-37ed5824db2e

License:

This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).

History

Date received : 22 September 2023

Date revision received : 2 February 2024

Date accepted : 12 February 2024

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