The Effect of Selected Herbal Medicines on Bone Turnover Markers: A Systematic Review and Meta-Analysis
-
Hanie Kheiridoost-Langaroodi
,
Seyed Kazem Shakouri
,
Mahdi Amirpour
,
Amir Mehdi Iranshahi
,
Azizeh Farshbaf-Khalili
Abstract
Objective: To evaluate systematically the therapeutic effects of five herbal medicines (curcumin, black seed, ginger, cinnamon, and flaxseed oil) on bone turnover markers as a primary outcome.
Materials and methods: A comprehensive systematic search of the literature was conducted in the electronic databases consisting of the Cochrane Library, MEDLINE, Web of Science, Scopus, Embase, ProQuest, and Google scholar, as well as SID, Magiran, and Irandoc for Persian literature up to December 2020. All Randomized controlled trials and quasi-experiments evaluated the impact of studied herbal medicines on bone turnovers of Bone Specific Alkaline Phosphatase (BSAP), osteocalcin, C-terminal Telopeptide type 1 Collagen (CTX-I), Deoxypyridinoline (DPD) were analyzed.
Results: Sixteen interventional studies comprised 968 participants included in systematic review. Ten of eligible studies with 603 participants included in meta-analysis. Curcumin, black seed and flaxseed did not have a significant effect on BSAP (SMD=-1.76, 95%CI: -6.85 to 3.33, p=0.50, I2=0.99, 6 trials, 241 participants), CTx (SMD=-0.17ng/mL, 95%CI:-0.43 to 0.09, p=0.21, I2=1.000, 5 trials, 216 participants), DPD (MD=0.82nmol/mmol, 95%CI:-0.05 to 1.68, p=0.06, I2=0.000, 2 trials, 67 participants), osteocalcin (SMD=-2.02ng/mL, 95%CI:-4.49 to 0.45, p=0.11, I2=0.79, Six trials, 229 participants). As secondary outcomes, femoral neck Bone Mineral Density (BMD) increased significantly (p=0.03, I2=0.12) but lumbar spine BMD didn’t differ (p=0.28, I2=0.97). Curcumin significantly increased total hip BMD (p<0.001, I2=0.12). QiangGuYin containing cinnamon as a combined Chinese medicine had significant effect on P1NP, β-CTx, and BMD.
Conclusion: Studied herbs except for QiangGuYin had no significant effects on bone turnover markers. Due to high heterogeneity between trials, further high-quality trials are suggested.
1. Chen X, Wang Z, Duan N, Zhu G, Schwarz EM, Xie C. Osteoblast-osteoclast interactions. Connect Tissue Res 2018; 59: 99-107.
2. Lorincz C, Manske SL, Zernicke R. Bone health: part 1, nutrition. Sports Health 2009; 1: 253-60.
3. Akkawi I, Zmerly H. Osteoporosis: Current Concepts. Joints 2018; 6: 122–7.
4. Clarke BL, Khosla S. Physiology of bone loss. Radiol Clin North Am 2010; 48: 483-95.
5. Higgins JPT, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011; 343: d5928.
6. Gupte PA, Giramkar SA, Harke SM, Kulkarni SK, Deshmukh AP, Hingorani LL, et al. Evaluation of the efficacy and safety of Capsule Longvida® Optimized Curcumin (solid lipid curcumin particles) in knee osteoarthritis: a pilot clinical study. J Inflamm Res 2019; 12: 145-52.
7. Hatefi M, Ahmadi MRH, Rahmani A, Dastjerdi MM, Asadollahi K. Effects of Curcumin on Bone Loss and Biochemical Markers of Bone Turnover in Patients with Spinal Cord Injury. World Neurosurg 2018; 114: e785-e91.
8. Khanizadeh F, Rahmani A, Asadollahi K, Ahmadi MRH. Combination therapy of curcumin and alendronate modulates bone turnover markers and enhances bone mineral density in postmenopausal women with osteoporosis. Arch Endocrinol Metab 2018; 62: 438-45.
9. Golombick T, Diamond TH, Badmaev V, Manoharan A, Ramakrishna R. The potential role of curcumin in patients with monoclonal gammopathy of undefined significance--its effect on paraproteinemia and the urinary N-telopeptide of type I collagen bone turnover marker. Clin Cancer Res 2009; 15: 5917-22.
10. Henrotin Y, Gharbi M, Dierckxsens Y, Priem F, Marty M, Seidel L, et al. Decrease of a specific biomarker of collagen degradation in osteoarthritis, Coll2-1, by treatment with highly bioavailable curcumin during an exploratory clinical trial. BMC Complement Altern Med 2014; 14: 159.
11. Valizadeh N, Zakeri HR, Amin Ansafi G, Shafiee A, Sarkhail P, Heshmat R, et al. Impact of Black seed (Nigella sativa) extract on bone turnover markers in postmenopausal women with osteoporosis. DARU Journal of Pharmaceutical Sciences 2010; 0: 20-5.
12. Shi ZY, Zhang XG, Li CW, Liu K, Liang BC, Shi XL. Effect of Traditional Chinese Medicine Product, QiangGuYin, on Bone Mineral Density and Bone Turnover in Chinese Postmenopausal Osteoporosis. Evid Based Complement Alternat Med 2017; 6062707.
13. Lucas EA, Wild RD, Hammond LJ, Khalil DA, Juma S, Daggy BP, et al. Flaxseed improves lipid profile without altering biomarkers of bone metabolism in postmenopausal women. J Clin Endocrinol Metab 2002; 87: 1527-32.
14. Brooks JD, Ward WE, Lewis JE, Hilditch J, Nickell L, Wong E, et al. Supplementation with flaxseed alters estrogen metabolism in postmenopausal women to a greater extent than does supplementation with an equal amount of soy. Am J Clin Nutr 2004; 79: 318-25.
15. Dodin S, Lemay A, Jacques H, Légaré F, Forest JC, Mâsse B. The effects of flaxseed dietary supplement on lipid profile, bone mineral density, and symptoms in menopausal women: a randomized, double-blind, wheat germ placebo-controlled clinical trial. J Clin Endocrinol Metab 2005; 90: 1390-7.
16. Griel AE, Kris-Etherton PM, Hilpert KF, Zhao G, West SG, Corwin RL. An increase in dietary n-3 fatty acids decreases a marker of bone resorption in humans. Nutr J 2007; 6: 2.
17. Aguilar CM, Sant'Ana CT, Costa AGV, Silva PI, Costa NMB. Comparative effects of brown and golden flaxseeds on body composition, inflammation and bone remodelling biomarkers in perimenopausal overweight women. Journal of Functional Foods 2017; 33: 166-75.
18. Rajaram S, Yip EL, Reghunathan R, Mohan S, Sabate J. Effect of Altering Dietary n-6: n-3 Polyunsaturated Fatty Acid Ratio with Plant and Marine-Based Supplement on Biomarkers of Bone Turnover in Healthy Adults. Nutrients 2017; 9:1162.
19. Mirfatahi M, Imani H, Tabibi H, Nasrollahi A, Hedayati M. Effects of Flaxseed Oil on Serum Bone Turnover Markers in Hemodialysis Patients: a Randomized Controlled Trial. Iran J Kidney Dis 2018; 12: 215-22.
20. Valizadeh N, Zakeri HR, Shafiee A, Sarkhail P, Heshmat R, Larijani B. The Effect of Nigella Sativa Extract on Biochemical Bone Markers in Osteopenic Postmenopausal Women. Iranian Journal of Endocrinology and Metabolism 2009; 10: 571-80.
21. Hasani-ranjbar Sh, Zahedi H, Fakhraee H, Taheri E, Laijani B. Efficacy and safety of Nigella sativa in the treatment of post-menopausal osteoporotic women: a randomized double-blind placebo-controlled trial. Maturitas 2015; 81: 163.
22. Al-Daghri NM, Yakout S, Al-Shehri E, Al-Fawaz H, Aljohani N, Al-Saleh Y. Inflammatory and bone turnover markers in relation to PTH and vitamin D status among Saudi postmenopausal women with and without osteoporosis. Int J Clin Exp Med 2014; 7: 2812-9.
23. Kuo TR, Chen CH. Bone biomarker for the clinical assessment of osteoporosis: recent developments and future perspectives. Biomark Res 2017; 5: 18.
24. Napoli N, Strollo R, Sprini D, Maddaloni E, Rini GB, Carmina E. Serum 25-OH Vitamin D in relation to Bone Mineral Density and Bone Turnover. Int
J Endocrinol 2014; 2014: 487463.
25. Ferreira A, Alho I, Casimiro S, Costa L. Bone remodeling markers and bone metastases: From cancer research to clinical implications. Bonekey Rep 2015; 4: 668.
26. Bharadwaj S, Naidu AG, Betageri GV, Prasadarao NV, Naidu AS. Milk ribonuclease-enriched lactoferrin induces positive effects on bone turnover markers in postmenopausal women. Osteoporos Int 2009; 20: 1603-11.
27. Pressman P, Clemens RA, Hayes AW. Bioavailability of micronutrients obtained from supplements and food: A survey and case study of the polyphenols. Toxicology Research and Application 2017; 1: 2397847317696366.
28. Jacobs DR, Tapsell LC. Food synergy: the key to a healthy diet. Proc Nutr Soc 2013; 72: 200-6.
29. Wan X, Wang W, Liu J, Tong T: Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol 2014; 14: 135.
30. Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, et al. Endocrine regulation of energy metabolism by the skeleton. Cell 2007; 130: 456-69.
31. Baim S, Miller PD. Assessing the clinical utility of serum CTX in postmenopausal osteoporosis and its use in predicting risk of osteonecrosis of the jaw. J Bone Miner Res 2009; 24: 561-74.
32. Seibel MJ. Biochemical markers of bone turnover: part I: biochemistry and variability. Clin Biochem Rev 2005; 26: 97-122.
33. 33. Kyd PA, Vooght KD, Kerkhoff F, Thomas E, Fairney A. Clinical usefulness of bone alkaline phosphatase in osteoporosis. Ann Clin Biochem 1998; 35: 717-25.
34. Garnero P, Vergnaud P, Hoyle N. Evaluation of a fully automated serum assay for total N-terminal propeptide of type I collagen in postmenopausal osteoporosis. Clin Chem 2008; 54: 188-96.
35. Halleen JM, Alatalo SL, Suominen H, Cheng S, Janckila AJ, Vaananen HK. Tartrate-resistant acid phosphatase 5b: a novel serum marker of bone resorption. J Bone Miner Res 2000; 15: 1337-45.
36. Nenonen A, Cheng S, Ivaska KK, Alatalo SL, Lehtimaki T, Schmidt-Gayk H, et al. Serum TRACP 5b is a useful marker for monitoring alendronate treatment: comparison with other markers of bone turnover. J Bone Miner Res 2005; 20: 1804-12.
37. Vaananen HK, Zhao H, Mulari M, Halleen JM. The cell biology of osteoclast function. J Cell Sci 2000; 113: 377-81.
38. Christgau S. Circadian variation in serum CrossLaps concentration is reduced in fasting individuals. Clin Chem 2000; 46: 431.
39. Shetty S, Kapoor N, Bondu JD, Thomas N, Paul TV. Bone turnover markers: Emerging tool in the management of osteoporosis. Indian J Endocrinol Metab 2016; 20: 846-52.
40. Shuid AN, Mohamed N, Mohamed IN, Othman F, Suhaimi F, Mohd Ramli ES, et al. Nigella sativa: A Potential Antiosteoporotic Agent. Evidence-Based Complementary and Alternative Medicine 2012; 696230.
41. Kania N, Widowati W, Dewi FRP, Christianto A, Setiawan B, Budhiparama N, Noor Z. Cinnamomum burmanini Blume increases bone turnover marker and induces tibia's granule formation in ovariectomized rats. J Ayurveda Integr Med 2018; 9: 20-6.
42. Tsuji-Naito K. Aldehydic components of cinnamon bark extract suppresses RANKL-induced osteoclastogenesis through NFATc1 downregulation. Bioorg Med Chem 2008; 16: 9176-83.
2. Lorincz C, Manske SL, Zernicke R. Bone health: part 1, nutrition. Sports Health 2009; 1: 253-60.
3. Akkawi I, Zmerly H. Osteoporosis: Current Concepts. Joints 2018; 6: 122–7.
4. Clarke BL, Khosla S. Physiology of bone loss. Radiol Clin North Am 2010; 48: 483-95.
5. Higgins JPT, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011; 343: d5928.
6. Gupte PA, Giramkar SA, Harke SM, Kulkarni SK, Deshmukh AP, Hingorani LL, et al. Evaluation of the efficacy and safety of Capsule Longvida® Optimized Curcumin (solid lipid curcumin particles) in knee osteoarthritis: a pilot clinical study. J Inflamm Res 2019; 12: 145-52.
7. Hatefi M, Ahmadi MRH, Rahmani A, Dastjerdi MM, Asadollahi K. Effects of Curcumin on Bone Loss and Biochemical Markers of Bone Turnover in Patients with Spinal Cord Injury. World Neurosurg 2018; 114: e785-e91.
8. Khanizadeh F, Rahmani A, Asadollahi K, Ahmadi MRH. Combination therapy of curcumin and alendronate modulates bone turnover markers and enhances bone mineral density in postmenopausal women with osteoporosis. Arch Endocrinol Metab 2018; 62: 438-45.
9. Golombick T, Diamond TH, Badmaev V, Manoharan A, Ramakrishna R. The potential role of curcumin in patients with monoclonal gammopathy of undefined significance--its effect on paraproteinemia and the urinary N-telopeptide of type I collagen bone turnover marker. Clin Cancer Res 2009; 15: 5917-22.
10. Henrotin Y, Gharbi M, Dierckxsens Y, Priem F, Marty M, Seidel L, et al. Decrease of a specific biomarker of collagen degradation in osteoarthritis, Coll2-1, by treatment with highly bioavailable curcumin during an exploratory clinical trial. BMC Complement Altern Med 2014; 14: 159.
11. Valizadeh N, Zakeri HR, Amin Ansafi G, Shafiee A, Sarkhail P, Heshmat R, et al. Impact of Black seed (Nigella sativa) extract on bone turnover markers in postmenopausal women with osteoporosis. DARU Journal of Pharmaceutical Sciences 2010; 0: 20-5.
12. Shi ZY, Zhang XG, Li CW, Liu K, Liang BC, Shi XL. Effect of Traditional Chinese Medicine Product, QiangGuYin, on Bone Mineral Density and Bone Turnover in Chinese Postmenopausal Osteoporosis. Evid Based Complement Alternat Med 2017; 6062707.
13. Lucas EA, Wild RD, Hammond LJ, Khalil DA, Juma S, Daggy BP, et al. Flaxseed improves lipid profile without altering biomarkers of bone metabolism in postmenopausal women. J Clin Endocrinol Metab 2002; 87: 1527-32.
14. Brooks JD, Ward WE, Lewis JE, Hilditch J, Nickell L, Wong E, et al. Supplementation with flaxseed alters estrogen metabolism in postmenopausal women to a greater extent than does supplementation with an equal amount of soy. Am J Clin Nutr 2004; 79: 318-25.
15. Dodin S, Lemay A, Jacques H, Légaré F, Forest JC, Mâsse B. The effects of flaxseed dietary supplement on lipid profile, bone mineral density, and symptoms in menopausal women: a randomized, double-blind, wheat germ placebo-controlled clinical trial. J Clin Endocrinol Metab 2005; 90: 1390-7.
16. Griel AE, Kris-Etherton PM, Hilpert KF, Zhao G, West SG, Corwin RL. An increase in dietary n-3 fatty acids decreases a marker of bone resorption in humans. Nutr J 2007; 6: 2.
17. Aguilar CM, Sant'Ana CT, Costa AGV, Silva PI, Costa NMB. Comparative effects of brown and golden flaxseeds on body composition, inflammation and bone remodelling biomarkers in perimenopausal overweight women. Journal of Functional Foods 2017; 33: 166-75.
18. Rajaram S, Yip EL, Reghunathan R, Mohan S, Sabate J. Effect of Altering Dietary n-6: n-3 Polyunsaturated Fatty Acid Ratio with Plant and Marine-Based Supplement on Biomarkers of Bone Turnover in Healthy Adults. Nutrients 2017; 9:1162.
19. Mirfatahi M, Imani H, Tabibi H, Nasrollahi A, Hedayati M. Effects of Flaxseed Oil on Serum Bone Turnover Markers in Hemodialysis Patients: a Randomized Controlled Trial. Iran J Kidney Dis 2018; 12: 215-22.
20. Valizadeh N, Zakeri HR, Shafiee A, Sarkhail P, Heshmat R, Larijani B. The Effect of Nigella Sativa Extract on Biochemical Bone Markers in Osteopenic Postmenopausal Women. Iranian Journal of Endocrinology and Metabolism 2009; 10: 571-80.
21. Hasani-ranjbar Sh, Zahedi H, Fakhraee H, Taheri E, Laijani B. Efficacy and safety of Nigella sativa in the treatment of post-menopausal osteoporotic women: a randomized double-blind placebo-controlled trial. Maturitas 2015; 81: 163.
22. Al-Daghri NM, Yakout S, Al-Shehri E, Al-Fawaz H, Aljohani N, Al-Saleh Y. Inflammatory and bone turnover markers in relation to PTH and vitamin D status among Saudi postmenopausal women with and without osteoporosis. Int J Clin Exp Med 2014; 7: 2812-9.
23. Kuo TR, Chen CH. Bone biomarker for the clinical assessment of osteoporosis: recent developments and future perspectives. Biomark Res 2017; 5: 18.
24. Napoli N, Strollo R, Sprini D, Maddaloni E, Rini GB, Carmina E. Serum 25-OH Vitamin D in relation to Bone Mineral Density and Bone Turnover. Int
J Endocrinol 2014; 2014: 487463.
25. Ferreira A, Alho I, Casimiro S, Costa L. Bone remodeling markers and bone metastases: From cancer research to clinical implications. Bonekey Rep 2015; 4: 668.
26. Bharadwaj S, Naidu AG, Betageri GV, Prasadarao NV, Naidu AS. Milk ribonuclease-enriched lactoferrin induces positive effects on bone turnover markers in postmenopausal women. Osteoporos Int 2009; 20: 1603-11.
27. Pressman P, Clemens RA, Hayes AW. Bioavailability of micronutrients obtained from supplements and food: A survey and case study of the polyphenols. Toxicology Research and Application 2017; 1: 2397847317696366.
28. Jacobs DR, Tapsell LC. Food synergy: the key to a healthy diet. Proc Nutr Soc 2013; 72: 200-6.
29. Wan X, Wang W, Liu J, Tong T: Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol 2014; 14: 135.
30. Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, et al. Endocrine regulation of energy metabolism by the skeleton. Cell 2007; 130: 456-69.
31. Baim S, Miller PD. Assessing the clinical utility of serum CTX in postmenopausal osteoporosis and its use in predicting risk of osteonecrosis of the jaw. J Bone Miner Res 2009; 24: 561-74.
32. Seibel MJ. Biochemical markers of bone turnover: part I: biochemistry and variability. Clin Biochem Rev 2005; 26: 97-122.
33. 33. Kyd PA, Vooght KD, Kerkhoff F, Thomas E, Fairney A. Clinical usefulness of bone alkaline phosphatase in osteoporosis. Ann Clin Biochem 1998; 35: 717-25.
34. Garnero P, Vergnaud P, Hoyle N. Evaluation of a fully automated serum assay for total N-terminal propeptide of type I collagen in postmenopausal osteoporosis. Clin Chem 2008; 54: 188-96.
35. Halleen JM, Alatalo SL, Suominen H, Cheng S, Janckila AJ, Vaananen HK. Tartrate-resistant acid phosphatase 5b: a novel serum marker of bone resorption. J Bone Miner Res 2000; 15: 1337-45.
36. Nenonen A, Cheng S, Ivaska KK, Alatalo SL, Lehtimaki T, Schmidt-Gayk H, et al. Serum TRACP 5b is a useful marker for monitoring alendronate treatment: comparison with other markers of bone turnover. J Bone Miner Res 2005; 20: 1804-12.
37. Vaananen HK, Zhao H, Mulari M, Halleen JM. The cell biology of osteoclast function. J Cell Sci 2000; 113: 377-81.
38. Christgau S. Circadian variation in serum CrossLaps concentration is reduced in fasting individuals. Clin Chem 2000; 46: 431.
39. Shetty S, Kapoor N, Bondu JD, Thomas N, Paul TV. Bone turnover markers: Emerging tool in the management of osteoporosis. Indian J Endocrinol Metab 2016; 20: 846-52.
40. Shuid AN, Mohamed N, Mohamed IN, Othman F, Suhaimi F, Mohd Ramli ES, et al. Nigella sativa: A Potential Antiosteoporotic Agent. Evidence-Based Complementary and Alternative Medicine 2012; 696230.
41. Kania N, Widowati W, Dewi FRP, Christianto A, Setiawan B, Budhiparama N, Noor Z. Cinnamomum burmanini Blume increases bone turnover marker and induces tibia's granule formation in ovariectomized rats. J Ayurveda Integr Med 2018; 9: 20-6.
42. Tsuji-Naito K. Aldehydic components of cinnamon bark extract suppresses RANKL-induced osteoclastogenesis through NFATc1 downregulation. Bioorg Med Chem 2008; 16: 9176-83.
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| Issue | Vol 16, No 1 (March 2022) | |
| Section | Review Articles | |
| DOI | https://doi.org/10.18502/jfrh.v16i1.8590 | |
| Keywords | ||
| Medicinal Plants Bone Remodeling Bone Density Meta-Analysis Systematic Review | ||
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How to Cite
1.
Kheiridoost-Langaroodi H, Shakouri SK, Amirpour M, Iranshahi AM, Farshbaf-Khalili A. The Effect of Selected Herbal Medicines on Bone Turnover Markers: A Systematic Review and Meta-Analysis. J Family Reprod Health. 2022;16(1):16-32.
