Effectiveness of a Nutraceutical, "Bone-Viva®"�, which is Composed of Generally Recognized as Safe (GRAS) Approved Ingredients in Stabilizing and Improving Bone Mineral Density in Patients with Osteopenia and Osteoporosis
Main Article Content
Abstract
Background: Osteopenia and osteoporosis are highly prevalent and often undertreated conditions in postmenopausal women, partly due to concerns about adverse effects and cost of pharmacologic therapies. Bone-Viva is a multi-ingredient nutraceutical formulation designed to support bone metabolism through nutritional and biochemical pathways.
Objective: To determine whether Bone-Viva stabilizes or improves bone mineral density (BMD) in women with osteopenia or osteoporosis and to evaluate its comparative and additive effects relative to denosumab, romosozumab, and combination therapy (Bone-Viva plus either denosumab or romosozumab).
Methods: This retrospective observational analysis included 51 women aged 54"90 years with osteopenia or osteoporosis. Patients received Bone-Viva monotherapy (n=12), denosumab (n=13), romosozumab (n=13), or Bone-Viva combined with either agent (n=13). Baseline and 1-year DEXA scans (Hologic Horizon W) assessed T-scores at the lumbar spine, femoral neck, and total hip. T-score changes were categorized as improved, stable, or declined using a ±0.1 threshold. Adverse events were recorded.
Results: The largest lumbar spine improvements of occurred with combination therapy T-score of (+0.20) and denosumab T-score of (+0.18), with 60"65% of patients improving. romosozumab produced a T-score +0.12 increase (48% improved), and Bone-Viva monotherapy showed a t-score +0.18 increase (42% improved). Femoral neck changes were modest for all groups. All groups showed excellent stability of (60%) in the femoral neck. At the total hip, all groups demonstrated small but consistent gains, led by combination therapy (+0.17). Bone-Viva stabilized T-scores in 45"48% of patients. One minor adverse event (transient stomach discomfort) was reported.
Conclusion: Bone-Viva was well tolerated and appeared to stabilize or modestly improve T-scores, particularly in patients with early bone loss. Combination therapy yielded the greatest overall improvements, suggesting potential synergistic benefit. Bone-Viva may offer a safe, economical adjunct or alternative for individuals seeking non-pharmacologic approaches to maintaining bone health. Larger prospective studies are warranted to validate these findings.
Article Details
How to Cite
YGLESIAS, Ronald et al.
Effectiveness of a Nutraceutical, "Bone-Viva®", which is Composed of Generally Recognized as Safe (GRAS) Approved Ingredients in Stabilizing and Improving Bone Mineral Density in Patients with Osteopenia and Osteoporosis.
Medical Research Archives, [S.l.], v. 13, n. 12, dec. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/7140>. Date accessed: 03 jan. 2026.
doi: https://doi.org/10.18103/mra.v13i12.7140.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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39. Kulczynski B, Gramza-Michalowska A. Carotenoids and bone health. Nutr Res. 2024;xx:xx-xx.
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48. Minguell JJ, Erices A, Conget P. Mesenchymal stem cells. Exp Biol Med (Maywood). 2001;226:507-520.
49. Minkin C. Tartrate-resistant acid phosphatase as an osteoclast marker. Calcif Tissue Int. 1982;34:285-290.
50. Murabajena S, Romana AA, Sindh C. Adipocyte differentiation in marrow mesenchymal stem cells. Cell Mol Life Sci. 2005;62:245-259.
51. Nielson CM, Srikanth P, Orwoll ES. Obesity and fracture risk. J Bone Miner Res. 2012;27:1-10.
52. Ormeno E, Baldy V, Ballini C, Fernandez C. Terpene variation across soils. J Chem Ecol. 2008;34:1219-1229.
53. Palermo A, Tuccinardi D, et al. Vitamin K and osteoporosis. Metabolism. 2017;70:57-66.
54. Paula-Fiel EL, Andersen ML, Gomes VA, et al. β-Caryophyllene attenuates pain in mice. Phytomedicine. 2016;23:356-367.
55. Pizzorno L. Nothing boring about boron. Integr Med (Encinitas). 2015;14:35-48.
56. Price CT, Koval KJ, Langford JR. Silicon and postmenopausal osteoporosis. Int J Endocrinol. 2013;2013:316783.
57. Rababah T, Al-Mahasneh M, Yang W, et al. Dietary boron and bone mineral density. J Trace Elem Med Biol. 2024:127300.
58. Raggatt LJ, Partridge NC. Cellular and molecular mechanisms of bone remodeling. J Biol Chem. 2010;285:25103-25108.
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60. Reid IR, Bolland MJ, Grey A. Vitamin D supplements and bone mineral density. Lancet. 2014;383:146-155.
61. Rondanelli M, Gasparri C, Peroni G, et al. Copper supplementation and bone metabolism. Nutrients. 2021;13:2767.
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63. Roux C, Reginster JY, et al. Vertebral fracture reduction with strontium ranelate. J Bone Miner Res. 2006;21:536-542.
64. Saltman PD, Strause LG. Calcium plus trace minerals slow spinal bone loss. J Nutr. 1994;124:1060-1064.
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71. Tu KN, et al. Osteoporosis: a review of treatment options. Pharm Ther. 2018;43:92-104.
72. Wang C, Li Y, Wang P, et al. Blood manganese and bone mineral density. PLoS One. 2022;17:e0268865.
73. Wang WJ, Li X, Zheng W, et al. Circulating zinc predicts bone mineral density. Bone. 2021;143:116090.
74. Weaver CM, Dawson-Hughes B, Lappe JM, et al. Calcium plus vitamin D and fracture risk. Osteoporos Int. 2016;27:367-376.
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76. Xie C, Zhang X, Zhu P, et al. Vitamin K supplementation and bone metabolism. Bone Joint Res. 2024;13:750-763.
77. Xu J, Song J, Zhao X, et al. Carotenoids and fracture risk. Oncotarget. 2017;8:48928-48936.
78. Yamaguchi M, Weitzmann MN, Murata T. Regucalcin suppresses osteoclastogenesis. Integr Biol (Camb). 2012;4:1251-1252.
79. Yamaguchi M, Zhu S, Zhang S, et al. UBIS109 prevents metastatic bone loss. Cell Tissue Res. 2014;357:245-252.
80. Yao P, Bennett D, Mafham M, et al. Vitamin D and calcium for fracture prevention. JAMA Netw Open. 2019;2:e1917789.
81. Zaidi M, Blair HC, Moonga BS, Abe E, Huang CL. Bone resorption and osteoblast therapeutics. J Bone Miner Res. 2003;18:599-609.
82. Zhang Z, Wang L, Chen X. Copper and bone metabolism. Bone Rep. 2024:101206.
83. Cummings SR, San Martin J, McClung MR, et al. denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361:756–65.
84. McClung MR, Lewiecki EM, Cohen SB, et al. denosumab in postmenopausal women with low bone mineral density. N Engl J Med. 2006;354:821–31.
85. Papapoulos S, Chapurlat R, Libanati C, et al. Five years of denosumab exposure in women with postmenopausal osteoporosis. J Bone Miner Res. 2012;27:694–701.
86. Cosman F, Crittenden DB, Adachi JD, et al. romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med. 2016;375:1532–43.
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88. Langdahl BL, Libanati C, Crittenden DB, et al. romosozumab followed by denosumab: results of the FRAME extension study. Osteoporos Int. 2017;28:2123–31.
2. Demontiero O, et al. Ther Adv Musculoskelet Dis. 2012;4(2):61 76.
3. Pouresmaeili F, et al. Ther Clin Risk Manag. 2018;14:2029 2049.
4. Gou J, et al. A nomogram for one-year risk of death after hip fracture. Front Med. 2025; 12:1500049.
5. TuKN et al. Pharm Ther. 2018;43(2):92 104
6. Kennel KA, Drake MT. Mayo Clin Proc. 2009;84(7):632 638.
7. Yamaguchi M, Levy RM. Exp Ther Med. 2016;12(6):3602 3606.
8. Rondanelli M, et al. J Trace Elem Med Biol. 2020;59:126577.
9. Jugdaohsingh R, et al. J Bone Miner Res. 2004;19(2):297 307.
10. Saltman PD, Strause LG. J Am Coll Nutr. 1993;12(4):384 389.
11. Holick MF. N Engl J Med. 2007;357(3):266 281.
12. Koshihara Y, et al. J Endocrinol. 2003;176(3):339 348.
13. Brennan TC, et al. Br J Pharmacol. 2009;157(7):1291 1300.
14. Akdas S, Ceylan MN, Yazici F, et al. Is zinc an important trace element on bone-related diseases and complications? A meta-analysis. Biol Trace Elem Res. 2021;199:3808-3821.
15. Baldy V, Ormeno E, Ballini C, Fernandez C. Production and diversity of volatile terpenes from plants on calcareous versus siliceous soils. J Chem Ecol. 2008;34:1219-1229.
16. Bartolini A, Ghelardini C, Galeotti N, Mannelli LCD, Mazzanti G. Local anesthetic activity of β-caryophyllene. Farmaco. 2001;56:387-389.
17. Blake GM, Fogelman I. Strontium ranelate: a novel treatment for postmenopausal osteoporosis. Clin Interv Aging. 2006;1(4):367-376.
18. Blair HC, Zaidi M, Moonga BS, Abe E, Huang CL. Osteoclastogenesis, bone resorption, and osteoblast-based therapeutics. J Bone Miner Res. 2003;18:599-609.
19. Chen M, Wu L, Jiang H, et al. Micronutrient intake and osteoporosis in hypertensive elderly. Front Nutr. 2024;11:1357439.
20. Chambers TJ, Fuller K. How are osteoclasts induced to resorb bone? Ann N Y Acad Sci. 2011;1240:1-7.
21. Chang J, Wang Z, Tang E, et al. Inhibition of osteoblastic bone formation by nuclear factor-κB. Nat Med. 2009;15:682-689.
22. Charkos TG, Kontogiorgis CA, Trikka FA, et al. Dietary β-carotene intake and fracture risk: a meta-analysis. Nutrients. 2020;12:2193.
23. Charkos TG, Skaperda Z, Tsekouras GE, et al. Carotenoid intake and osteoporosis risk: a propensity-matched analysis. J Health Popul Nutr. 2025;44:xx-xx.
24. Chawla M, Yadav P, Shinde DB. Analgesic and anti-inflammatory activity of caryophyllene oxide. Indian J Pharmacol. 2014;46:475-481.
25. Cong B, Xu Y, Chen Y, et al. Combined calcium and vitamin D improves bone mineral density in postmenopausal osteoporosis. J Bone Miner Res. 2025;40:xx-xx.
26. Cortez M, Carmo LS, Rogero MM, Borelli P, Fock RA. High-fat diet increases IL-1, IL-6, TNF-α via NF-κB in bone marrow stromal cells. Inflammation. 2016;39:370-383.
27. Cui A, Zhao J, Wang H, et al. Dietary copper intake and bone mineral density in US adults. PLoS One. 2024;19:e0296228.
28. Fan D, Liu L, et al. Curcumin prevents diabetic osteoporosis via osteogenic and angiogenic pathways. J Diabetes Res. 2022;2022:9476132.
29. Fung EB, Ritchie J, Kaplan P, et al. Zinc supplementation improves bone density in thalassemia. Am J Clin Nutr. 2013;98:960-971.
30. Gao SS, Wang J, Qin L, et al. Effects of β-carotene on osteoporosis: a systematic review and meta-analysis. Menopause. 2023;30:xxx-xxx.
31. Gertsch J, Leonti M, Raduner S, et al. Beta-caryophyllene is a dietary cannabinoid. Proc Natl Acad Sci U S A. 2008;105:9099-9104.
32. Gharibi B, Abraham AA, Ham J, Evans BA. Adenosine receptor activation influences mesenchymal stem cell osteogenesis. J Bone Miner Res. 2011;26:2112-2124.
33. Ghelardini C, Galeotti N, Mannelli LCD, Mazzanti G, Bartolini A. Local anesthetic activity of β-caryophyllene. Farmaco. 2001;56:387-389.
34. Gou J, Shi K, Dai R, Wang J, Li Y. A nomogram for one-year risk of death after hip fracture. Front Med. 2025;12:1500049.
35. Hu L, Chen X, et al. Combined vitamin K and calcium on bone mineral density. J Orthop Surg Res. 2021;16:592.
36. Hu M, Zhang X, et al. Dietary copper and bone mineral density. Medicine (Baltimore). 2025;104:e43777.
37. Iwamoto I, Takeda T, et al. Longitudinal effects of vitamin K2 on bone mineral density. Maturitas. 1999;31:161-168.
38. Katsuyama M, Mizoguchi H, Kuwahata H, et al. CB2 involvement in β-caryophyllene–induced antinociception. Eur J Pain. 2013;17:664-675.
39. Kulczynski B, Gramza-Michalowska A. Carotenoids and bone health. Nutr Res. 2024;xx:xx-xx.
40. Leslie WD, Rubin MR, Schwartz AV, Kanis JA. Type 2 diabetes and bone. J Bone Miner Res. 2012;27:2231-2237.
41. Li Y, Li A, Strait K, et al. Endogenous TNF-α reduces bone mass via NF-κB inhibition. J Bone Miner Res. 2007;22:646-655.
42. Li Z, Kawashima T, Kato K, et al. Silicon absorption from mineral water and effects on bone metabolism. Nutr J. 2010;9:44.
43. Liu C, Chen L, et al. Calcium and vitamin D supplementation in postmenopausal osteoporosis. Food Funct. 2020;11:1920-1930.
44. Macdonald HM, Hardcastle AC, Jugdaohsingh R, et al. Silicon–estrogen interactions in bone health. J Nutr Health Aging. 2012;16:128-134.
45. Ma ML, Shen Q, et al. Vitamin K2 in osteoporosis: a meta-analysis. Front Public Health. 2022;10:895067.
46. Martin YS, Salamano M, Cardenas RD, et al. Antinociceptive activity of β-caryophyllene. Eur J Pharmacol. 2016;775:52-64.
47. Meunier PJ, Roux C, Ortolani S, et al. Strontium ranelate reduces vertebral fracture risk in postmenopausal women. N Engl J Med. 2004;350:459-468.
48. Minguell JJ, Erices A, Conget P. Mesenchymal stem cells. Exp Biol Med (Maywood). 2001;226:507-520.
49. Minkin C. Tartrate-resistant acid phosphatase as an osteoclast marker. Calcif Tissue Int. 1982;34:285-290.
50. Murabajena S, Romana AA, Sindh C. Adipocyte differentiation in marrow mesenchymal stem cells. Cell Mol Life Sci. 2005;62:245-259.
51. Nielson CM, Srikanth P, Orwoll ES. Obesity and fracture risk. J Bone Miner Res. 2012;27:1-10.
52. Ormeno E, Baldy V, Ballini C, Fernandez C. Terpene variation across soils. J Chem Ecol. 2008;34:1219-1229.
53. Palermo A, Tuccinardi D, et al. Vitamin K and osteoporosis. Metabolism. 2017;70:57-66.
54. Paula-Fiel EL, Andersen ML, Gomes VA, et al. β-Caryophyllene attenuates pain in mice. Phytomedicine. 2016;23:356-367.
55. Pizzorno L. Nothing boring about boron. Integr Med (Encinitas). 2015;14:35-48.
56. Price CT, Koval KJ, Langford JR. Silicon and postmenopausal osteoporosis. Int J Endocrinol. 2013;2013:316783.
57. Rababah T, Al-Mahasneh M, Yang W, et al. Dietary boron and bone mineral density. J Trace Elem Med Biol. 2024:127300.
58. Raggatt LJ, Partridge NC. Cellular and molecular mechanisms of bone remodeling. J Biol Chem. 2010;285:25103-25108.
59. Reginster JY, Bruyere O, et al. Strontium ranelate reduces non-vertebral fractures. J Clin Endocrinol Metab. 2005;90:2816-2822.
60. Reid IR, Bolland MJ, Grey A. Vitamin D supplements and bone mineral density. Lancet. 2014;383:146-155.
61. Rondanelli M, Gasparri C, Peroni G, et al. Copper supplementation and bone metabolism. Nutrients. 2021;13:2767.
62. Rondanelli M, Faliva MA, Peroni G, et al. Silicon as an essential micronutrient for bone. Exp Biol Med. 2021;246:827-838.
63. Roux C, Reginster JY, et al. Vertebral fracture reduction with strontium ranelate. J Bone Miner Res. 2006;21:536-542.
64. Saltman PD, Strause LG. Calcium plus trace minerals slow spinal bone loss. J Nutr. 1994;124:1060-1064.
65. Seeman E, Vellas B, et al. Strontium ranelate reduces fractures in elderly women. Bone. 2010;46:1038-1044.
66. Strait K. See Li Y.
67. Su Y, Li W, et al. Supplemental mineral ions for bone regeneration. Bone Res. 2023;11:34.
68. Takada I, Kouzmenko AP, Kato S. Wnt signaling in mesenchymal stem cell differentiation. Endocrinology. 2009;150:2042-2048.
69. Tang BMP, Eslick GD, Nowson C, et al. Calcium with or without vitamin D for fracture prevention. Lancet. 2007;370:657-666.
70. Tohidian M, Sarrafzadeh J, et al. Dietary copper and bone health. Biol Trace Elem Res. 2025;xx:xx-xx.
71. Tu KN, et al. Osteoporosis: a review of treatment options. Pharm Ther. 2018;43:92-104.
72. Wang C, Li Y, Wang P, et al. Blood manganese and bone mineral density. PLoS One. 2022;17:e0268865.
73. Wang WJ, Li X, Zheng W, et al. Circulating zinc predicts bone mineral density. Bone. 2021;143:116090.
74. Weaver CM, Dawson-Hughes B, Lappe JM, et al. Calcium plus vitamin D and fracture risk. Osteoporos Int. 2016;27:367-376.
75. Wright NC, Looker AC, Saag KG, et al. The burden of osteoporosis in the United States. J Bone Miner Res. 2014;29:2520-2526.
76. Xie C, Zhang X, Zhu P, et al. Vitamin K supplementation and bone metabolism. Bone Joint Res. 2024;13:750-763.
77. Xu J, Song J, Zhao X, et al. Carotenoids and fracture risk. Oncotarget. 2017;8:48928-48936.
78. Yamaguchi M, Weitzmann MN, Murata T. Regucalcin suppresses osteoclastogenesis. Integr Biol (Camb). 2012;4:1251-1252.
79. Yamaguchi M, Zhu S, Zhang S, et al. UBIS109 prevents metastatic bone loss. Cell Tissue Res. 2014;357:245-252.
80. Yao P, Bennett D, Mafham M, et al. Vitamin D and calcium for fracture prevention. JAMA Netw Open. 2019;2:e1917789.
81. Zaidi M, Blair HC, Moonga BS, Abe E, Huang CL. Bone resorption and osteoblast therapeutics. J Bone Miner Res. 2003;18:599-609.
82. Zhang Z, Wang L, Chen X. Copper and bone metabolism. Bone Rep. 2024:101206.
83. Cummings SR, San Martin J, McClung MR, et al. denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361:756–65.
84. McClung MR, Lewiecki EM, Cohen SB, et al. denosumab in postmenopausal women with low bone mineral density. N Engl J Med. 2006;354:821–31.
85. Papapoulos S, Chapurlat R, Libanati C, et al. Five years of denosumab exposure in women with postmenopausal osteoporosis. J Bone Miner Res. 2012;27:694–701.
86. Cosman F, Crittenden DB, Adachi JD, et al. romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med. 2016;375:1532–43.
87. Saag KG, Petersen J, Brandi ML, et al. romosozumab or alendronate for fracture prevention in women with osteoporosis. N Engl J Med. 2017;377:1417–27.
88. Langdahl BL, Libanati C, Crittenden DB, et al. romosozumab followed by denosumab: results of the FRAME extension study. Osteoporos Int. 2017;28:2123–31.