Osteoporosis and Leptin: A Systematic Review
Abstract
Background: Leptin has a great effect on bone through direct or indirect involvement in bone remodeling. Considering the ambiguities that exist regarding the effect of leptin on bone and bone-related diseases including osteoporosis, in this study, we aimed to conduct a systematic review of various studies on the effect of leptin on osteoporosis, which may find an answer to the existing ambiguities.
Methods: The search was performed to review studies on the effects of leptin on osteoporosis by using several databases including Scopus, PubMed, Web of Science, and Google Scholar. Electronic searches were conducted on 5 Jan 2023. There was no limit on the publication date of the articles. The risk of bias for the animal study was assessed with the CAMARADES checklist, and the study quality assessment was also assessed based on the guidelines for in vivo experiments (ARRIVE). In this study, the risk of bias (quality) of human studies was assessed using the quality assessment checklists by NHLBI.
Results: Overall, 34 articles were included for data extraction and quality assessment. Overall, 27 human studies and seven animal studies were included in the article. The results of most of the studies conducted in this study showed that leptin has a physiological role in maintaining bone mass and better bone quality and reduces bone marrow adipogenesis and increases bone mineral density (BMD). As plasma leptin levels increased, BMD values or bone formation biomarkers increased.
Conclusion: Leptin has an inhibitory role against bone resorption and increasing osteoprotegerin (OPG) levels, which, as a result, maintains bone density and reduces osteoclast activity, and has a positive relationship with increasing osteocalcin.
1. Carey JJ, Chih-Hsing Wu P, Bergin D (2022). Risk assessment tools for osteoporosis and fractures in 2022. Best Pract Res Clin Rheumatol, 36(3):101775.
2. LeBoff MS, Greenspan SL, Insogna KL, et al (2022). The clinician's guide to prevention and treatment of osteoporosis. Osteoporos Int, 33(10):2049-102.
3. Eastell R, O'Neill TW, Hofbauer LC, et al (2016). Postmenopausal osteoporosis. Nat Rev Dis Primers, 2:16069.
4. Men Z, Huang C, Xu M, Ma J, Wan L, Huang J, et al (2022). Zhuanggu Zhitong Capsule alleviates postmenopausal osteoporosis in ovariectomized rats by regulating autophagy through AMPK/mTOR signaling pathway. Ann Transl Med, 10(16):900.
5. Armas LA, Recker RR (2012). Pathophysiology of osteoporosis: new mechanistic insights. Endocrinol Metab Clin North Am, 41(3):475-86.
6. Colaianni G, Brunetti G, Faienza MF, Colucci S, Grano M (2014). Osteoporosis and obesity: Role of Wnt pathway in human and murine models. World J Orthop, 5(3):242-6.
7. Sadie-Van Gijsen H, Crowther NJ, et al (2013). The interrelationship between bone and fat: from cellular see-saw to endocrine reciprocity. Cell Mol Life Sci, 70(13):2331-49.
8. López-Gómez JJ, Pérez-Castrillón JL, García de Santos I, et al (2022). Influence of Obesity on Bone Turnover Markers and Fracture Risk in Postmenopausal Women. Nutrients, 14(8):1617.
9. Chen XX, Yang T (2015). Roles of leptin in bone metabolism and bone diseases. J Bone Miner Metab, 33(5):474-85.
10. Reid IR, Baldock PA, Cornish J (2018). Effects of Leptin on the Skeleton. Endocr Rev, 39(6):938-59.
11. Zhang Y, Huang X, Sun K, Li M, Wang X, Han T, et al (2022). The Potential Role of Serum IGF-1 and Leptin as Biomarkers: Towards Screening for and Diagnosing Postmenopausal Osteoporosis. J Inflamm Res, 15:533-43.
12. Liu K, Liu P, Liu R, Wu X, Cai M (2015). Relationship between serum leptin levels and bone mineral density: a systematic review and meta-analysis. Clin Chim Acta, 444:260-263.
13. Shu L, Fu Y, Sun H (2022). The association between common serum adipokines levels and postmenopausal osteoporosis: A meta-analysis. J Cell Mol Med, 26(15):4333-42.
14. Page MJ, McKenzie JE, Bossuyt PM, et al (2021). The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ, 372:n71.
15. National Institutes for Health (2021). Study quality assessment tool for observational cohort and cross-sectional studies. https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools
16. Macleod MR, O'Collins T, Howells DW, et al (2004). Pooling of animal experimental data reveals influence of study design and publication bias. Stroke, 35(5):1203-8.
17. Percie du Sert N, Ahluwalia A, Alam S, et al (2020). Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0. PLoS Biol, 18(7):e3000411.
18. Ye G, Huang Y, Yin L, Wang J, Huang X, Bin X (2022). Association between LEPR polymorphism and susceptibility of osteoporosis in Chinese Mulao people. Artif Cells Nanomed Biotechnol, 50(1):10-16.
19. Zhang ZM, Jiang LS, Jiang SD, Dai LY (2009). Osteogenic potential and responsiveness to leptin of mesenchymal stem cells between postmenopausal women with osteoarthritis and osteoporosis. J Orthop Res, 27(8):1067-73.
20. Wang X, Zhang Y, Qi B, et al (2022). IL-6 and Leptin Are Potential Biomarkers for Osteoporotic Fracture Risk Assessment and Prediction of Postmenopausal Women with Low Bone Mass: A Follow-Up Study Using a Regional Sample Cohort. Oxid Med Cell Longev, 2022:8691830.
21. Ye XL, Lu CF (2013). Association of polymorphisms in the leptin and leptin receptor genes with inflammatory mediators in patients with osteoporosis. Endocrine, 44(2):481-8.
22. Sun P, Zhang Y, Wei Z, Wang Z, Guo S, Lin Y (2020). Effect of Qing'e Decoction on Leptin/Leptin Receptor and Bone Metabolism in Naturally Aging Rats. Evid Based Complement Alternat Med, 2020:2532081.
23. Zhang X, Xiaofeng LV, Zhang Y, Jiao X, Chen B (2013). Propranolol prevents osteoporosis and up-regulates Leptin in ovariectomized rats. Iran J Pharm Res, 12(3):557-62.
24. Zheng B, Jiang J, Chen Y, et al (2017). Leptin Overexpression in Bone Marrow Stromal Cells Promotes Periodontal Regeneration in a Rat Model of Osteoporosis. J Periodontol, 88(8):808-818.
25. Shaarawy M, Abassi AF, Hassan H, Salem ME (2003). Relationship between serum leptin concentrations and bone mineral density as well as biochemical markers of bone turnover in women with postmenopausal osteoporosis. Fertil Steril, 79(4):919-24.
26. Nakamura Y, Nakano M, Suzuki T, et al (2020). Two adipocytokines, leptin and adiponectin, independently predict osteoporotic fracture risk at different bone sites in postmenopausal women. Bone, 137:115404.
27. Koçyiǧit H, Bal S, Atay A, et al (2013). Plasma leptin values in postmenopausal women with osteoporosis. Bosn J Basic Med Sci, 13(3):192-6.
28. Odabaşi E, Ozata M, Turan M, et al (2000). Plasma leptin concentrations in postmenopausal women with osteoporosis. Eur J Endocrinol, 142(2):170-3.
29. Lee HJ, Kim H, Ku SY, et al (2014). Association between polymorphisms in leptin, leptin receptor, and β-adrenergic receptor genes and bone mineral density in postmenopausal Korean women. Menopause, 21(1):67-73.
30. Hess R, Pino AM, Ríos S, Fernández M, Rodríguez JP (2005). High affinity leptin receptors are present in human mesenchymal stem cells (MSCs) derived from control and osteoporotic donors. J Cell Biochem, 94(1):50-7.
31. Yamauchi M, Sugimoto T, Yamaguchi T, et al (2001). Plasma leptin concentrations are associated with bone mineral density and the presence of vertebral fractures in postmenopausal women. Clin Endocrinol (Oxf), 55(3):341-7.
32. Mpalaris V, Anagnostis P, Anastasilakis AD, et al (2016). Serum leptin, adiponectin and ghrelin concentrations in post-menopausal women: Is there an association with bone mineral density? Maturitas, 88:32-6.
33. Rhie YJ, Lee KH, Chung SC, et al (2010). Effects of body composition, leptin, and adiponectin on bone mineral density in prepubertal girls. J Korean Med Sci, 25(8):1187-90.
34. Şahin G, Polat G, Baoiş S, et al (2003). Body composition, bone mineral density, and circulating leptin levels in postmenopausal Turkish women. Rheumatol Int, 23(2):87-91.
35. Roux C, Arabi A, Porcher R, Garnero P (2003). Serum leptin as a determinant of bone resorption in healthy postmenopausal women. Bone, 33(5):847-52.
36. Głogowska-Szeląg J, Kos-Kudła B, Marek B, et al (2019). Assessment of selected adipocytokines in obese women with postmenopausal osteoporosis. Endokrynol Pol, 70(6):478-83.
37. Saber LM, Mahran HN, Baghdadi HH, et al (2015). Interrelationship between bone turnover markers, calciotropic hormones and leptin in obese Saudi children. Eur Rev Med Pharmacol Sci, 19(22):4332-43.
38. Prouteau S, Benhamou L, Courteix D (2006). Relationships between serum leptin and bone markers during stable weight, weight reduction and weight regain in male and female judoists. Eur J Endocrinol, 154(3):389-95.
39. Hipmair G, Böhler N, Maschek W, et al (2010). Serum leptin is correlated to high turnover in osteoporosis. Neuro Endocrinol Lett, 31(1):155-60.
40. Dennison EM, Syddall HE, Fall CH, et al (2004). Plasma leptin concentration and change in bone density among elderly men and women: the Hertfordshire Cohort Study. Calcif Tissue Int, 74(5):401-6.
41. Mohiti-Ardekani J, Soleymani-Salehabadi H, Owlia MB, Mohiti A (2014). Relationships between serum adipocyte hormones (adiponectin, leptin, resistin), bone mineral density and bone metabolic markers in osteoporosis patients, J Bone Miner Metab, 32(4):400-4.
42. Thomas T, Burguera B, Melton Iii LJ, et al (2001). Role of serum leptin, insulin, and estrogen levels as potential mediators of the relationship between fat mass and bone mineral density in men versus women. Bone, 29(2):114-20.
43. Crabbe P, Goemaere S, Zmierczak H, et al (2006). Are serum leptin and the Gln223Arg polymorphism of the leptin receptor determinants of bone homeostasis in elderly men? Eur J Endocrinol,154(5):707-14.
44. Anagnostis P, Vakalopoulou S, Charizopoulou M, et al (2013). Is there any association between leptin levels and bone mineral density in haemophiliac men? Arch Med Sci, 9(3):459-65.
45. Lorentzon M, Landin K, Mellström D, Ohlsson C (2006). Leptin is a negative independent predictor of areal BMD and cortical bone size in young adult Swedish men. J Bone Miner Res, 21(12):1871-8.
46. Pobeha P, Ukropec J, Skyba P, et al (2011). Relationship between osteoporosis and adipose tissue leptin and osteoprotegerin in patients with chronic obstructive pulmonary disease. Bone, 48(5):1008-14.
47. Ahmed HH, Morcos NY, Eskander EF, et al (2012). Potential role of leptin against glucocorticoid-induced secondary osteoporosis in adult female rats. Eur Rev Med Pharmacol Sci, 16(10):1446-52.
48. Stavropoulou A, Christopoulou GE, Anastassopoulos G, et al (2005). Alteration in serum leptin correlates with alterations in serum N-telopeptide of collagen type I and serum osteocalcin during the progression of osteoporosis in ovariectomized rats. Clin Chem Lab Med, 43(12):1359-65.
49. Reich MS, Jarvis JP, Silva MJ, Cheverud JM (2008). Genetic relationships between obesity and osteoporosis in LGXSM recombinant inbred mice. Genet Res (Camb), 90(5):433-44.
50. McCabe IC, Fedorko A, Myers MG, Jr., Leinninger G, Scheller E, McCabe LR (2019). Novel leptin receptor signaling mutants identify location and sex-dependent modulation of bone density, adiposity, and growth. J Cell Biochem, 120(3):4398-4408.
2. LeBoff MS, Greenspan SL, Insogna KL, et al (2022). The clinician's guide to prevention and treatment of osteoporosis. Osteoporos Int, 33(10):2049-102.
3. Eastell R, O'Neill TW, Hofbauer LC, et al (2016). Postmenopausal osteoporosis. Nat Rev Dis Primers, 2:16069.
4. Men Z, Huang C, Xu M, Ma J, Wan L, Huang J, et al (2022). Zhuanggu Zhitong Capsule alleviates postmenopausal osteoporosis in ovariectomized rats by regulating autophagy through AMPK/mTOR signaling pathway. Ann Transl Med, 10(16):900.
5. Armas LA, Recker RR (2012). Pathophysiology of osteoporosis: new mechanistic insights. Endocrinol Metab Clin North Am, 41(3):475-86.
6. Colaianni G, Brunetti G, Faienza MF, Colucci S, Grano M (2014). Osteoporosis and obesity: Role of Wnt pathway in human and murine models. World J Orthop, 5(3):242-6.
7. Sadie-Van Gijsen H, Crowther NJ, et al (2013). The interrelationship between bone and fat: from cellular see-saw to endocrine reciprocity. Cell Mol Life Sci, 70(13):2331-49.
8. López-Gómez JJ, Pérez-Castrillón JL, García de Santos I, et al (2022). Influence of Obesity on Bone Turnover Markers and Fracture Risk in Postmenopausal Women. Nutrients, 14(8):1617.
9. Chen XX, Yang T (2015). Roles of leptin in bone metabolism and bone diseases. J Bone Miner Metab, 33(5):474-85.
10. Reid IR, Baldock PA, Cornish J (2018). Effects of Leptin on the Skeleton. Endocr Rev, 39(6):938-59.
11. Zhang Y, Huang X, Sun K, Li M, Wang X, Han T, et al (2022). The Potential Role of Serum IGF-1 and Leptin as Biomarkers: Towards Screening for and Diagnosing Postmenopausal Osteoporosis. J Inflamm Res, 15:533-43.
12. Liu K, Liu P, Liu R, Wu X, Cai M (2015). Relationship between serum leptin levels and bone mineral density: a systematic review and meta-analysis. Clin Chim Acta, 444:260-263.
13. Shu L, Fu Y, Sun H (2022). The association between common serum adipokines levels and postmenopausal osteoporosis: A meta-analysis. J Cell Mol Med, 26(15):4333-42.
14. Page MJ, McKenzie JE, Bossuyt PM, et al (2021). The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ, 372:n71.
15. National Institutes for Health (2021). Study quality assessment tool for observational cohort and cross-sectional studies. https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools
16. Macleod MR, O'Collins T, Howells DW, et al (2004). Pooling of animal experimental data reveals influence of study design and publication bias. Stroke, 35(5):1203-8.
17. Percie du Sert N, Ahluwalia A, Alam S, et al (2020). Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0. PLoS Biol, 18(7):e3000411.
18. Ye G, Huang Y, Yin L, Wang J, Huang X, Bin X (2022). Association between LEPR polymorphism and susceptibility of osteoporosis in Chinese Mulao people. Artif Cells Nanomed Biotechnol, 50(1):10-16.
19. Zhang ZM, Jiang LS, Jiang SD, Dai LY (2009). Osteogenic potential and responsiveness to leptin of mesenchymal stem cells between postmenopausal women with osteoarthritis and osteoporosis. J Orthop Res, 27(8):1067-73.
20. Wang X, Zhang Y, Qi B, et al (2022). IL-6 and Leptin Are Potential Biomarkers for Osteoporotic Fracture Risk Assessment and Prediction of Postmenopausal Women with Low Bone Mass: A Follow-Up Study Using a Regional Sample Cohort. Oxid Med Cell Longev, 2022:8691830.
21. Ye XL, Lu CF (2013). Association of polymorphisms in the leptin and leptin receptor genes with inflammatory mediators in patients with osteoporosis. Endocrine, 44(2):481-8.
22. Sun P, Zhang Y, Wei Z, Wang Z, Guo S, Lin Y (2020). Effect of Qing'e Decoction on Leptin/Leptin Receptor and Bone Metabolism in Naturally Aging Rats. Evid Based Complement Alternat Med, 2020:2532081.
23. Zhang X, Xiaofeng LV, Zhang Y, Jiao X, Chen B (2013). Propranolol prevents osteoporosis and up-regulates Leptin in ovariectomized rats. Iran J Pharm Res, 12(3):557-62.
24. Zheng B, Jiang J, Chen Y, et al (2017). Leptin Overexpression in Bone Marrow Stromal Cells Promotes Periodontal Regeneration in a Rat Model of Osteoporosis. J Periodontol, 88(8):808-818.
25. Shaarawy M, Abassi AF, Hassan H, Salem ME (2003). Relationship between serum leptin concentrations and bone mineral density as well as biochemical markers of bone turnover in women with postmenopausal osteoporosis. Fertil Steril, 79(4):919-24.
26. Nakamura Y, Nakano M, Suzuki T, et al (2020). Two adipocytokines, leptin and adiponectin, independently predict osteoporotic fracture risk at different bone sites in postmenopausal women. Bone, 137:115404.
27. Koçyiǧit H, Bal S, Atay A, et al (2013). Plasma leptin values in postmenopausal women with osteoporosis. Bosn J Basic Med Sci, 13(3):192-6.
28. Odabaşi E, Ozata M, Turan M, et al (2000). Plasma leptin concentrations in postmenopausal women with osteoporosis. Eur J Endocrinol, 142(2):170-3.
29. Lee HJ, Kim H, Ku SY, et al (2014). Association between polymorphisms in leptin, leptin receptor, and β-adrenergic receptor genes and bone mineral density in postmenopausal Korean women. Menopause, 21(1):67-73.
30. Hess R, Pino AM, Ríos S, Fernández M, Rodríguez JP (2005). High affinity leptin receptors are present in human mesenchymal stem cells (MSCs) derived from control and osteoporotic donors. J Cell Biochem, 94(1):50-7.
31. Yamauchi M, Sugimoto T, Yamaguchi T, et al (2001). Plasma leptin concentrations are associated with bone mineral density and the presence of vertebral fractures in postmenopausal women. Clin Endocrinol (Oxf), 55(3):341-7.
32. Mpalaris V, Anagnostis P, Anastasilakis AD, et al (2016). Serum leptin, adiponectin and ghrelin concentrations in post-menopausal women: Is there an association with bone mineral density? Maturitas, 88:32-6.
33. Rhie YJ, Lee KH, Chung SC, et al (2010). Effects of body composition, leptin, and adiponectin on bone mineral density in prepubertal girls. J Korean Med Sci, 25(8):1187-90.
34. Şahin G, Polat G, Baoiş S, et al (2003). Body composition, bone mineral density, and circulating leptin levels in postmenopausal Turkish women. Rheumatol Int, 23(2):87-91.
35. Roux C, Arabi A, Porcher R, Garnero P (2003). Serum leptin as a determinant of bone resorption in healthy postmenopausal women. Bone, 33(5):847-52.
36. Głogowska-Szeląg J, Kos-Kudła B, Marek B, et al (2019). Assessment of selected adipocytokines in obese women with postmenopausal osteoporosis. Endokrynol Pol, 70(6):478-83.
37. Saber LM, Mahran HN, Baghdadi HH, et al (2015). Interrelationship between bone turnover markers, calciotropic hormones and leptin in obese Saudi children. Eur Rev Med Pharmacol Sci, 19(22):4332-43.
38. Prouteau S, Benhamou L, Courteix D (2006). Relationships between serum leptin and bone markers during stable weight, weight reduction and weight regain in male and female judoists. Eur J Endocrinol, 154(3):389-95.
39. Hipmair G, Böhler N, Maschek W, et al (2010). Serum leptin is correlated to high turnover in osteoporosis. Neuro Endocrinol Lett, 31(1):155-60.
40. Dennison EM, Syddall HE, Fall CH, et al (2004). Plasma leptin concentration and change in bone density among elderly men and women: the Hertfordshire Cohort Study. Calcif Tissue Int, 74(5):401-6.
41. Mohiti-Ardekani J, Soleymani-Salehabadi H, Owlia MB, Mohiti A (2014). Relationships between serum adipocyte hormones (adiponectin, leptin, resistin), bone mineral density and bone metabolic markers in osteoporosis patients, J Bone Miner Metab, 32(4):400-4.
42. Thomas T, Burguera B, Melton Iii LJ, et al (2001). Role of serum leptin, insulin, and estrogen levels as potential mediators of the relationship between fat mass and bone mineral density in men versus women. Bone, 29(2):114-20.
43. Crabbe P, Goemaere S, Zmierczak H, et al (2006). Are serum leptin and the Gln223Arg polymorphism of the leptin receptor determinants of bone homeostasis in elderly men? Eur J Endocrinol,154(5):707-14.
44. Anagnostis P, Vakalopoulou S, Charizopoulou M, et al (2013). Is there any association between leptin levels and bone mineral density in haemophiliac men? Arch Med Sci, 9(3):459-65.
45. Lorentzon M, Landin K, Mellström D, Ohlsson C (2006). Leptin is a negative independent predictor of areal BMD and cortical bone size in young adult Swedish men. J Bone Miner Res, 21(12):1871-8.
46. Pobeha P, Ukropec J, Skyba P, et al (2011). Relationship between osteoporosis and adipose tissue leptin and osteoprotegerin in patients with chronic obstructive pulmonary disease. Bone, 48(5):1008-14.
47. Ahmed HH, Morcos NY, Eskander EF, et al (2012). Potential role of leptin against glucocorticoid-induced secondary osteoporosis in adult female rats. Eur Rev Med Pharmacol Sci, 16(10):1446-52.
48. Stavropoulou A, Christopoulou GE, Anastassopoulos G, et al (2005). Alteration in serum leptin correlates with alterations in serum N-telopeptide of collagen type I and serum osteocalcin during the progression of osteoporosis in ovariectomized rats. Clin Chem Lab Med, 43(12):1359-65.
49. Reich MS, Jarvis JP, Silva MJ, Cheverud JM (2008). Genetic relationships between obesity and osteoporosis in LGXSM recombinant inbred mice. Genet Res (Camb), 90(5):433-44.
50. McCabe IC, Fedorko A, Myers MG, Jr., Leinninger G, Scheller E, McCabe LR (2019). Novel leptin receptor signaling mutants identify location and sex-dependent modulation of bone density, adiposity, and growth. J Cell Biochem, 120(3):4398-4408.
| Files | ||
| Issue | Vol 53 No 1 (2024) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v53i1.14686 | |
| Keywords | ||
| Leptin Bone losses Bone resorption | ||
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How to Cite
1.
Mohammadi SM, Saniee N, Borzoo T, Radmanesh E. Osteoporosis and Leptin: A Systematic Review. Iran J Public Health. 2024;53(1):93-103.
