Anti-Osteoporosis Treatment Alleviates Osteoarthritis Symptoms and Partially Reverses Disease Progression

Ziyang Feng , Heyong Yin , Yufei Ding , Xun Sun , Tao Zhang , Ai Guo

Orthopaedic Surgery ›› 2025, Vol. 17 ›› Issue (8) : 2467 -2478.

PDF
Orthopaedic Surgery ›› 2025, Vol. 17 ›› Issue (8) : 2467 -2478. DOI: 10.1111/os.70115
RESEARCH ARTICLE

Anti-Osteoporosis Treatment Alleviates Osteoarthritis Symptoms and Partially Reverses Disease Progression

Author information +
History +
PDF

Abstract

Objective: Osteoarthritis (OA) and osteoporosis (OP) are highly prevalent in postmenopausal women; however, their relationship remains complex and controversial. This study aimed to investigate whether anti-OP treatment alleviates osteoarthritis symptoms and reverses disease progression.

Methods: This prospective clinical study enrolled 30 postmenopausal women diagnosed with OP and concomitant knee OA who visited our outpatient clinic between January and June 2023. Patients received anti-osteoporotic treatment comprising calcium carbonate, vitamin D3, and alendronate (ALN). BMD, WOMAC, and VAS scores were assessed at 6 and 12 months. In animal studies, OP was induced in rats by ovariectomy, followed by OA induction via anterior cruciate ligament sectioning and meniscectomy. ALN treatment was administered for 8 weeks, and evaluations of behavior, macroscopic appearance, pathology, and subchondral bone microstructure were performed 8 weeks after OA induction. One-way ANOVA was used for multiple group comparisons, and Spearman's rank correlation was used to assess associations.

Results: Clinical outcomes demonstrated that one-year anti-OP therapy achieved dual therapeutic benefits: a 9.3% increase in bone mineral density (BMD) was accompanied by a 36.54% reduction in knee OA symptoms. Statistical analysis revealed a strong positive correlation between BMD improvement and symptomatic relief (r = 0.76, p < 0.05). In the animal model, OP markedly accelerated OA progression, leading to more severe cartilage damage, as confirmed by symptoms, macroscopic cartilage appearance, and histological evaluations. Micro-CT analysis revealed abnormal subchondral bone microarchitecture in OP animals. Notably, ALN treatment partially reversed OA progression, as evidenced by reduced cartilage degeneration, improved subchondral bone microstructure, and enhanced bone remodeling.

Conclusion: Anti-OP treatment alleviates knee OA symptoms in OP patients. Postmenopausal OP accelerates OA progression, while anti-OP therapy can partially reverse this effect. These findings highlights the importance of anti-OP treatment in managing both conditions.

Keywords

alendronate / bone remodeling / cartilage / osteoarthritis / osteoporosis

Cite this article

Download citation ▾
Ziyang Feng, Heyong Yin, Yufei Ding, Xun Sun, Tao Zhang, Ai Guo. Anti-Osteoporosis Treatment Alleviates Osteoarthritis Symptoms and Partially Reverses Disease Progression. Orthopaedic Surgery, 2025, 17(8): 2467-2478 DOI:10.1111/os.70115

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

P. P. Geusens and J. P. van den Bergh, “Osteoporosis and Osteoarthritis: Shared Mechanisms and Epidemiology,” Current Opinion in Rheumatology 28, no. 2 (2016): 97-103.

[2]

E. M. Curtis, R. van der Velde, R. J. Moon, et al., “Epidemiology of Fractures in the United Kingdom 1988-2012: Variation With Age, Sex, Geography, Ethnicity and Socioeconomic Status,” Bone 87 (2016): 19-26.

[3]

A. Dubin, “Managing Osteoarthritis and Other Chronic Musculoskeletal Pain Disorders,” Medical Clinics of North America 100, no. 1 (2016): 143-150.

[4]

J. Martel-Pelletier, A. J. Barr, F. M. Cicuttini, et al., “Osteoarthritis,” Nature Reviews Disease Primers 2 (2016): 16072.

[5]

K. Johnson, S. Zhu, M. S. Tremblay, et al., “A Stem Cell-Based Approach to Cartilage Repair,” Science (New York, N.Y.) 336, no. 6082 (2012): 717-721.

[6]

M. Fernández-Moreno, I. Rego-Pérez, and F. J. Blanco, “Is Osteoarthritis a Mitochondrial Disease? What Is the Evidence,” Current Opinion in Rheumatology 34, no. 1 (2022): 46-53.

[7]

I. E. Bultink and W. F. Lems, “Osteoarthritis and Osteoporosis: What Is the Overlap?,” Current Rheumatology Reports 15, no. 5 (2013): 328.

[8]

P. A. Berry, R. A. Maciewicz, F. M. Cicuttini, M. D. Jones, C. J. Hellawell, and A. E. Wluka, “Markers of Bone Formation and Resorption Identify Subgroups of Patients With Clinical Knee Osteoarthritis Who Have Reduced Rates of Cartilage Loss,” Journal of Rheumatology 37, no. 6 (2010): 1252-1259.

[9]

M. B. Goldring and S. R. Goldring, “Articular Cartilage and Subchondral Bone in the Pathogenesis of Osteoarthritis,” Annals of the New York Academy of Sciences 1192 (2010): 230-237.

[10]

L. L. Laslett, S. R. Kingsbury, E. M. Hensor, M. A. Bowes, and P. G. Conaghan, “Effect of Bisphosphonate Use in Patients With Symptomatic and Radiographic Knee Osteoarthritis: Data From the Osteoarthritis Initiative,” Annals of the Rheumatic Diseases 73, no. 5 (2014): 824-830.

[11]

G. Zhen and X. Cao, “Targeting TGFβ Signaling in Subchondral Bone and Articular Cartilage Homeostasis,” Trends in Pharmacological Sciences 35, no. 5 (2014): 227-236.

[12]

S. Chen, T. He, Y. Zhong, et al., “Roles of Focal Adhesion Proteins in Skeleton and Diseases,” Acta Pharmaceutica Sinica B 13, no. 3 (2023): 998-1013.

[13]

L. L. Laslett, D. A. Doré, S. J. Quinn, et al., “Zoledronic Acid Reduces Knee Pain and Bone Marrow Lesions Over 1 Year: A Randomised Controlled Trial,” Annals of the Rheumatic Diseases 71, no. 8 (2012): 1322-1328.

[14]

T. Nishii, S. Tamura, T. Shiomi, H. Yoshikawa, and N. Sugano, “Alendronate Treatment for Hip Osteoarthritis: Prospective Randomized 2-Year Trial,” Clinical Rheumatology 32, no. 12 (2013): 1759-1766.

[15]

M. Ehrnsperger, S. Taheri, P. Pann, A. F. Schilling, and S. Grässel, “Differential Effects of Alendronate on Chondrocytes, Cartilage Matrix and Subchondral Bone Structure in Surgically Induced Osteoarthritis in Mice,” Scientific Reports 14, no. 1 (2024): 25026.

[16]

S. Zhu, K. Chen, Y. Lan, N. Zhang, R. Jiang, and J. Hu, “Alendronate Protects Against Articular Cartilage Erosion by Inhibiting Subchondral Bone Loss in Ovariectomized Rats,” Bone 53, no. 2 (2013): 340-349.

[17]

S. D. Vasikaran, M. Miura, R. Pikner, H. P. Bhattoa, and E. Cavalier, “Practical Considerations for the Clinical Application of Bone Turnover Markers in Osteoporosis,” Calcified Tissue International 112, no. 2 (2023): 148-157.

[18]

N. Yousefzadeh, K. Kashfi, S. Jeddi, and A. Ghasemi, “Ovariectomized Rat Model of Osteoporosis: A Practical Guide,” EXCLI Journal 19 (2020): 89-107.

[19]

A. Ratneswaran and F. Beier, “An Approach Towards Accountability: Suggestions for Increased Reproducibility in Surgical Destabilization of Medial Meniscus (DMM) Models,” Osteoarthritis and Cartilage 25, no. 11 (2017): 1747-1750.

[20]

J. Hu, B. Zhou, X. Lin, et al., “Impaired Bone Strength and Bone Microstructure in a Novel Early-Onset Osteoporotic Rat Model With a Clinically Relevant PLS3 Mutation,” eLife 12 (2023): e80365.

[21]

S. Zhu, J. Zhu, G. Zhen, et al., “Subchondral Bone Osteoclasts Induce Sensory Innervation and Osteoarthritis Pain,” Journal of Clinical Investigation 129, no. 3 (2019): 1076-1093.

[22]

J. R. Wagner, T. Taguchi, J. Y. Cho, C. Charavaryamath, and D. J. Griffon, “Evaluation of Stem Cell Therapies in a Bilateral Patellar Tendon Injury Model in Rats,” Journal of Visualized Experiments 133 (2018): 56810.

[23]

N. Gerwin, A. M. Bendele, S. Glasson, and C. S. Carlson, “The OARSI Histopathology Initiative—Recommendations for Histological Assessments of Osteoarthritis in the Rat,” Osteoarthritis and Cartilage 18, no. Suppl 3 (2010): S24-S34.

[24]

M. L. Bouxsein, S. K. Boyd, B. A. Christiansen, R. E. Guldberg, K. J. Jepsen, and R. Müller, “Guidelines for Assessment of Bone Microstructure in Rodents Using Micro-Computed Tomography,” Journal of Bone and Mineral Research 25, no. 7 (2010): 1468-1486.

[25]

J. A. van der Sluijs, R. G. Geesink, A. J. van der Linden, S. K. Bulstra, R. Kuyer, and J. Drukker, “The Reliability of the Mankin Score for Osteoarthritis,” Journal of Orthopaedic Research 10, no. 1 (1992): 58-61.

[26]

W. Hu, Y. Chen, C. Dou, and S. Dong, “Microenvironment in Subchondral Bone: Predominant Regulator for the Treatment of Osteoarthritis,” Annals of the Rheumatic Diseases 80, no. 4 (2021): 413-422.

[27]

T. Hügle and J. Geurts, “What Drives Osteoarthritis?-Synovial Versus Subchondral Bone Pathology,” Rheumatology (Oxford, England) 56, no. 9 (2017): 1461-1471.

[28]

S. R. Goldring and M. B. Goldring, “Changes in the Osteochondral Unit During Osteoarthritis: Structure, Function and Cartilage-Bone Crosstalk,” Nature Reviews Rheumatology 12, no. 11 (2016): 632-644.

[29]

Z. Cui, J. Crane, H. Xie, et al., “Halofuginone Attenuates Osteoarthritis by Inhibition of TGF-β Activity and H-Type Vessel Formation in Subchondral Bone,” Annals of the Rheumatic Diseases 75, no. 9 (2016): 1714-1721.

[30]

B. Kovács, E. Vajda, and E. E. Nagy, “Regulatory Effects and Interactions of the Wnt and OPG-RANKL-RANK Signaling at the Bone-Cartilage Interface in Osteoarthritis,” International Journal of Molecular Sciences 20, no. 18 (2019): 4653.

[31]

J. Liang, L. Liu, H. Feng, et al., “Therapeutics of Osteoarthritis and Pharmacological Mechanisms: A Focus on RANK/RANKL Signaling,” Biomedicine & Pharmacotherapy 167 (2023): 115646.

[32]

J. Lu, D. Hu, Y. Zhang, C. Ma, L. Shen, and B. Shuai, “Current Comprehensive Understanding of Denosumab (The RANKL Neutralizing Antibody) in the Treatment of Bone Metastasis of Malignant Tumors, Including Pharmacological Mechanism and Clinical Trials,” Frontiers in Oncology 13 (2023): 1133828.

[33]

M. Bellido, L. Lugo, J. A. Roman-Blas, et al., “Improving Subchondral Bone Integrity Reduces Progression of Cartilage Damage in Experimental Osteoarthritis Preceded by Osteoporosis,” Osteoarthritis and Cartilage 19, no. 10 (2011): 1228-1236.

[34]

L. Hu, X. Xie, H. Xue, et al., “MiR-1224-5p Modulates Osteogenesis by Coordinating Osteoblast/Osteoclast Differentiation via the Rap1 Signaling Target ADCY2,” Experimental & Molecular Medicine 54, no. 7 (2022): 961-972.

[35]

T. D. Spector, P. G. Conaghan, J. C. Buckland-Wright, et al., “Effect of Risedronate on Joint Structure and Symptoms of Knee Osteoarthritis: Results of the BRISK Randomized, Controlled Trial [ISRCTN01928173],” Arthritis Research & Therapy 7, no. 3 (2005): R625-R633.

[36]

C. O. Bingham, J. C. Buckland-Wright, P. Garnero, et al., “Risedronate Decreases Biochemical Markers of Cartilage Degradation but Does Not Decrease Symptoms or Slow Radiographic Progression in Patients With Medial Compartment Osteoarthritis of the Knee: Results of the Two-Year Multinational Knee Osteoarthritis Structural Arthritis Study,” Arthritis & Rheumatism 54, no. 11 (2006): 3494-3507.

[37]

K. Huang and H. Cai, “The Interplay Between Osteoarthritis and Osteoporosis: Mechanisms, Implications, and Treatment Considerations - A Narrative Review,” Experimental Gerontology 197 (2024): 112614.

[38]

I. Coskun Benlidayi, “Bone Health in Autoimmune Inflammatory Rheumatic Diseases,” in Translational Autoimmunity, ed. N. Rezaei (Academic Press, 2023), 9-26.

[39]

D. B. Burr and M. A. Gallant, “Bone Remodelling in Osteoarthritis,” Nature Reviews Rheumatology 8, no. 11 (2012): 665-673.

RIGHTS & PERMISSIONS

2025 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.

AI Summary AI Mindmap
PDF

21

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/