Osteoporosis is the most common bone disease both worldwide and in the United States, and generally remains subclinical until the occurrence of fracture. With osteoporotic fractures being a substantial source of morbidity and mortality, effective therapies for slowing the decline of bone density in affected individuals are much needed. The standard therapy of osteoporosis may include medication, fall prevention, smoking cessation, avoidance of excess alcohol intake, calcium, and weight-bearing exercise. This article reviews complementary or integrative approaches with evidence for use in osteoporosis. This includes strontium, choline-stabilized orthosilicic acid, isoflavones (including ipriflavone and soy isoflavones), vitamin D, and vitamin K.
LaneNE. Epidemiology, etiology, and diagnosis of osteoporosis. Am J Obstet Gynecol, 2006; 194:S3–S11.
3.
SalariN, GhasemiH, MohammadiL, et al.The global prevalence of osteoporosis in the world: A comprehensive systematic review and meta-analysis. J Orthop Surg Res, 2021; 16(1):20.
4.
ReidIR. A broader strategy for osteoporosis interventions. Nat Rev Endocrinol, 2020; 16:333–339.
5.
LeBoffMS, GreenspanSL, InsognaKL, et al.The clinician’s guide to prevention and treatment of osteoporosis. Osteoporosis International, 2022; 33:2049–2102.
6.
Guzon-IllescasO, Perez FernandezE, Crespí VillariasN, et al.Mortality after osteoporotic hip fracture: Incidence, trends, and associated factors. J Orthop Surg Res, 2019; 14.
7.
SchiniM, JohanssonH, HarveyNC, et al.An overview of the use of the fracture risk assessment tool (FRAX) in osteoporosis. J Endocrinol Invest, 2024; 47:501–511.
WilliamsC, SapraA. Osteoporosis Markers. Stat Pearls Publishing: Treasure Island, FL; 2023.
10.
KosteckaM. The role of healthy diet in the prevention of osteoporosis in perimenopausal period. Pak J Med Sci, 2014; 30:763.
11.
SampsonHW. Alcohol and other factors affecting osteoporosis risk in women. Alcohol Res Health, 2002; 26:292.
12.
Rodríguez-GómezI, MañasA, Losa-ReynaJ, et al.Associations between sedentary time, physical activity and bone health among older people using compositional data analysis. PLoS One, 2018; 13.
13.
LinZ, ShiG, LiaoX, et al.Correlation between sedentary activity, physical activity and bone mineral density and fat in America: National Health and Nutrition Examination Survey, 2011–2018. Sci Rep, 2023; 13:1–9.
14.
WangD, YangY. The relationship between serum 25-hydroxyvitamin d levels and osteoporosis in postmenopausal women. Clin Interv Aging, 2023; 18:619.
15.
Anonymous. Management of osteoporosis in postmenopausal women: The 2021 position statement of The North American Menopause Society. Menopause, 2021; 28:973–997.
16.
KanisJA, CooperC, RizzoliR, et al.European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporosis International, 2019; 30:3.
17.
WolfeRR. The underappreciated role of muscle in health and disease. Am J Clin Nutr, 2006; 84:475–482.
18.
LeeDY, ShinS. Association of sarcopenia with osteopenia and osteoporosis in community-dwelling older Korean adults: A Cross-Sectional Study. J Clin Med, 2022; 11:129.
19.
HuangT, LiC, ChenF, et al.Prevalence and risk factors of osteosarcopenia: A systematic review and meta-analysis. BMC Geriatr, 2023; 23.
20.
QaseemA, HicksLA, Etxeandia-IkobaltzetaI, et al.Pharmacologic Treatment of primary osteoporosis or low bone mass to prevent fractures in adults: A living clinical guideline from the American College of Physicians. Ann Intern Med, 2023; 176:224–239.
21.
LeeSH, GongHS, KimT-H, et al.Position statement: Drug holiday in osteoporosis treatment with bisphosphonates in South Korea. J Bone Metab, 2015; 22:167.
KalraS, JainV. Dental complications and management of patients on bisphosphonate therapy: A review article. J Oral Biol Craniofac Res, 2013; 3:25.
24.
KołodziejskaB, StępieńN, KolmasJ. The influence of strontium on bone tissue metabolism and its application in osteoporosis treatment. Int J Mol Sci, 2021; 22:22.
25.
YangL, KangN, YangJC, et al.Drug efficacies on bone mineral density and fracture rate for the treatment of postmenopausal osteoporosis: A network meta-analysis. Eur Rev Med Pharmacol Sci, 2019; 23:2640–2668.
26.
ColletteJ, BruyèreO, KaufmanJM, et al.Vertebral anti-fracture efficacy of strontium ranelate according to pre-treatment bone turnover. Osteoporosis International, 2010; 21:233.
27.
GenuisSJ, SchwalfenbergGK. Picking a bone with contemporary osteoporosis management: Nutrient strategies to enhance skeletal integrity. Clin Nutrition, 2007; 26:193–207.
28.
KanisJA, JohanssonH, OdenA, et al.A meta-analysis of the effect of strontium ranelate on the risk of vertebral and non-vertebral fracture in postmenopausal osteoporosis and the interaction with FRAX(®). Osteoporos Int, 2011; 22:2347–2355.
29.
MeunierPJ, RouxC, SeemanE, et al.The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med, 2004; 350:459–468.
30.
ReginsterJY, SeemanE, De VernejoulMC, et al.Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) Study. J Clin Endocrinol Metab, 2005; 90:2816–2822.
31.
BarrionuevoP, KapoorE, AsiN, et al.Efficacy of pharmacological therapies for the prevention of fractures in postmenopausal women: A network meta-analysis. J Clin Endocrinol Metab, 2019; 104:1623–1630.
32.
RingeJD, DohertyJG. Absolute risk reduction in osteoporosis: Assessing treatment efficacy by number needed to treat. Rheumatol Int, 2010; 30:863–869.
33.
O’DonnellS, CranneyA, WellsGA, et al.Strontium ranelate for preventing and treating postmenopausal osteoporosis. Cochrane Database Syst Rev, 2006; 2006.
34.
CurtisEM, CooperC, HarveyNC. Cardiovascular safety of calcium, magnesium and strontium: What does the evidence say? Aging Clin Exp Res, 2021; 33:479–494.
35.
ErvitiJ, GorrichoJ, SaizLC, et al.Rethinking the appraisal and approval of drugs for fracture prevention. Front Pharmacol, 2017; 8:265.
36.
MariaS, SwansonMH, EnderbyLT, et al.Melatonin-micronutrients Osteopenia Treatment Study (MOTS): A translational study assessing melatonin, strontium (citrate), vitamin D3 and vitamin K2 (MK7) on bone density, bone marker turnover and health related quality of life in postmenopausal osteopenic women following a one-year double-blind RCT and on osteoblast-osteoclast co-cultures. Aging (Albany NY), 2017; 9:256.
37.
CabreraWE, SchrootenI, De BroeME, et al.Strontium and Bone. J Bone Mineral Res, 1999; 14:661–668.
38.
PilmaneM, Salma-AncaneK, LocaD, et al.Strontium and strontium ranelate: Historical review of some of their functions. Materials Science and Engineering: C, 2017; 78:1222–1230.
39.
RondanelliM, FalivaMA, PeroniG, et al.Silicon: A neglected micronutrient essential for bone health. Exp Biol Med, 2021; 246:1500.
40.
PritchardA, RobisonC, NguyenT, et al.Silicon supplementation affects mineral metabolism but not bone density or strength in male broilers. PLoS One, 2020; 15:e0243007.
41.
MillucciL, MinettiM, OrlandiniM, et al.Beer promotes differentiation and mineralization of human osteoblastic cells: Role of silicon. J Funct Foods, 2019; 54:109–118.
42.
SpectorTD, CalommeMR, AndersonSH, et al.Choline-stabilized orthosilicic acid supplementation as an adjunct to Calcium/Vitamin D3 stimulates markers of bone formation in osteopenic females: A randomized, placebo-controlled trial. BMC Musculoskelet Disord, 2008; 9:85.
43.
LiuHY, ZhangCQ. Effects of daidzein on messenger ribonucleic acid expression of gonadotropin receptors in chicken ovarian follicles. Poult Sci, 2008; 87:541–545.
44.
KřížováL, DadákováK, KašparovskáJ, et al.Isoflavones. Molecules, 2019; 24.
45.
ReginsterJYL. Ipriflavone: Pharmacological properties and usefulness in postmenopausal osteoporosis. Bone Miner, 1993; 23:223–232.
46.
ZhangX, ShuXO, LiH, et al.Prospective Cohort Study of soy food consumption and risk of bone fracture among postmenopausal women. Arch Intern Med, 2005; 165:1890–1895.
47.
De AloysioD, GambaccianiM, AltieriP, et al.Bone density changes in postmenopausal women with the administration of ipriflavone alone or in association with low-dose ERT. Gynecol Endocrinol, 1997; 11:289–293.
48.
OhtaH, KomukaiS, MakitaK, et al.Effects of 1-year ipriflavone treatment on lumbar bone mineral density and bone metabolic markers in postmenopausal women with low bone mass. Horm Res, 1999; 51:178–183.
49.
AgnusdeiD, BufalinoL. Efficacy of ipriflavone in established osteoporosis and long-term safety. Calcif Tissue Int, 1997; 61.
50.
MaugeriD, PanebiancoP, RussoMS, et al.Ipriflavone-treatment of senile osteoporosis: Results of a multicenter, double-blind clinical trial of 2 years. Arch Gerontol Geriatr, 1994; 19:253–263.
51.
HuQ, LongC, WuD, et al.The efficacy and safety of ipriflavone in postmenopausal women with osteopenia or osteoporosis: A systematic review and meta-analysis. Pharmacol Res, 2020; 159
52.
AlexandersenP, ToussaintA, ChristiansenC, et al.Ipriflavone in the treatment of postmenopausal osteoporosis: A randomized controlled trial. JAMA, 2001; 285:1482–1488.
53.
MaDF, QinLQ, WangPY, et al.Soy isoflavone intake increases bone mineral density in the spine of menopausal women: Meta-analysis of randomized controlled trials. Clin Nutr, 2008; 27:57–64.
54.
LiuJ, HoSC, SuY, et al.Effect of long-term intervention of soy isoflavones on bone mineral density in women: A meta-analysis of randomized controlled trials. Bone, 2009; 44:948–953.
55.
SoungDY, PatadeA, KhalilDA, et al.Soy protein supplementation does not cause lymphocytopenia in postmenopausal women. Nutr J, 2006; 5:1–6.
56.
PikeJW, ChristakosS. Biology and mechanisms of action of the vitamin D hormone. Endocrinol Metab Clin North Am, 2017; 46:815.
57.
LibonF, CavalierE, NikkelsAF. Skin color is relevant to vitamin D synthesis. Dermatology, 2013; 227:250–254.
58.
NevilleJJ, PalmieriT, YoungAR. Physical determinants of vitamin D photosynthesis: A review. JBMR Plus, 2021; 5.
59.
SpeddingS. Vitamin D and depression: A systematic review and meta-analysis comparing studies with and without biological flaws. Nutrients, 2014; 6:1501.
60.
ManojP, DerwinR, GeorgeS. What is the impact of daily oral supplementation of vitamin D3 (cholecalciferol) plus calcium on the incidence of hip fracture in older people? A systematic review and meta‐analysis. Int J Older People Nurs, 2023; 18.
61.
ReidIR, BollandMJ, GreyA. Effects of vitamin D supplements on bone mineral density: A systematic review and meta-analysis. Lancet, 2014; 383:146–155.
62.
WeaverCM, AlexanderDD, BousheyCJ, et al.Calcium plus vitamin D supplementation and risk of fractures: An updated meta-analysis from the National Osteoporosis Foundation. Osteoporosis International, 2016; 27:367.
63.
ZhaoJG, ZengXT, WangJ, et al.Association between calcium or vitamin D supplementation and fracture incidence in community-dwelling older adults: A systematic review and meta-analysis. Jama, 2017; 318:2466.
64.
MavarM, SorícTS, BagarícbagarícE, et al.The power of vitamin D: Is the future in precision nutrition through personalized supplementation plans? Nutrients, 2024; 16:1176.
65.
ChevalleyT, BrandiML, CashmanKD, et al.Role of vitamin D supplementation in the management of musculoskeletal diseases: Update from an European Society of Clinical and Economical Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) working group. Aging Clinical and Experimental Research, 2022; 34:2603–2623.
66.
MaML, MaZJ, HeYL, et al.Efficacy of vitamin K2 in the prevention and treatment of postmenopausal osteoporosis: A systematic review and meta-analysis of randomized controlled trials. Front Public Health, 2022; 10.
PalmerCR, KochH, ShindeS, et al.Development of a vitamin K database for commercially available food in Australia. Front Nutr, 2021; 8:753059.
69.
TarvainenM, FabritiusM, YangB. Determination of vitamin K composition of fermented food. Food Chem, 2019; 275:515–522.
70.
CockayneS, AdamsonJ, Lanham-NewS, et al.Vitamin K and the prevention of fractures: Systematic review and meta-analysis of randomized controlled trials. Arch Intern Med, 2006; 166:1256–1261.
71.
BoothSL, DallalG, SheaMK, et al.Effect of vitamin K supplementation on bone loss in elderly men and women. J Clin Endocrinol Metab, 2008; 93:1217–1223.
72.
BinkleyN, HarkeJ, KruegerD, et al.Vitamin K treatment reduces undercarboxylated osteocalcin but does not alter bone turnover, density, or geometry in healthy postmenopausal North American women. J Bone Miner Res, 2009; 24:983–991.
73.
StevensonM, Lloyd-JonesM, PapaioannouD. Vitamin K to prevent fractures in older women: Systematic review and economic evaluation. Health Technol Assess, 2009; 13.
74.
KnapenMHJ, DrummenNE, SmitE, et al.Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporos Int, 2013; 24:2499–2507.
75.
ZhouM, HanS, ZhangW, et al.Efficacy and safety of vitamin K2 for postmenopausal women with osteoporosis at a long-term follow-up: Meta-analysis and systematic review. J Bone Miner Metab, 2022; 40.
76.
WeilbaecherKN, GuiseTA, McCauleyLK. Cancer to bone: A fatal attraction. Nat Rev Cancer, 2011; 11:411–425.
77.
BeckBR, DalyRM, SinghMAF, et al.Exercise and Sports Science Australia (ESSA) position statement on exercise prescription for the prevention and management of osteoporosis. J Sci Med Sport, 2017; 20:438–445.
78.
MorinSN, FeldmanS, FunnellL, et al.Clinical practice guideline for management of osteoporosis and fracture prevention in Canada: 2023 update. CMAJ Canadian Medical Association Journal, 2023; 195:E1333–E1348.
79.
IinoC, ShimoyamaT, IinoK, et al.Daidzein intake is associated with Equol producing status through an increase in the intestinal bacteria responsible for Equol production. Nutrients, 2019:11.
80.
DailyJW, KoBS, RyukJ, et al.Equol decreases hot flashes in postmenopausal women: A systematic review and meta-analysis of Randomized Clinical Trials. J Med Food, 2019; 22:127–139.
