Abstract
Background. Nutrients and nutraceuticals are widely used as supplements for osteoporosis prevention or as adjunctive therapy, but the evidence from human studies is inconsistent.
Objective. To review data on micro-and macronutrients and nutraceuticals that influence bone mineral density (BMD), turnover, microarchitecture, or fracture risk, contextualizing findings within guidelines.
Methods. Narrative review of randomized controlled trials (RCTs), meta-analyses, and extensive observational studies published through August 19, 2025. Outcomes prioritized include BMD, fractures, bone turnover markers (BTMs), and indices of bone quality such as trabecular bone score (TBS).
Results and discussion. Substantial evidence supports correcting low calcium (Ca) intake and reduced vitamin D levels, the only supplements consistently endorsed by guidelines for osteoporosis management. Moderate evidence includes collagen peptides, vitamin K2 (MK-7), with site-specific but mixed results; alkali salts improve turnover and BMD, resveratrol shows small gains, and prebiotics enhance Ca absorption. There is weak evi- dence available for omega-3 fatty acids, iso avones, green tea catechins, prunes, hesperidin, probiotics, minerals, and silicon. Main botanicals and carotenoids remain experimental. Safety profiles vary across compounds, and long term safety data are insufficient for most nutraceuticals.
Conclusions. Nutrients and nutraceuticals can complement lifestyle and pharmacother-apy when tailored to address specific deficiencies or phenotypes. Large, long-term RCTs with safety, fracture outomes, and microarchitectural endpoints are needed to clarify efficacy and guide evidence-based recommendations.
Introduction
Osteoporosis affects hundreds of millions of people worldwide and is characterized by reduced bone mineral density (BMD) and deterioration of bone microarchitecture, leading to an increased risk of fragility fractures. Current clinical guidelines recommend adequate calcium (Ca) and vitamin D3 (cholecalciferol, hereafter vit D), weight-bearing and resistance exercise, fall-prevention strategies, and appropriate pharmacological therapy when indicated [1,2].
Nevertheless, many patients seek additional nutrients and nutraceuticals – bioactive, food-derived compounds that may exert physiological effects beyond basic nutrition – as complementary measures to “bridge the gap” between diet and medication. Their widespread use reflects both the commercial expansion of the nutraceutical market and the perception of supplements as safer or more “natural” alternatives. However, the supporting evidence is heterogeneous, ranging from large-scale RCTs and meta-analyses to small, short-term trials, and the clinical relevance of many findings remains uncertain.
This narrative review synthesizes available human data across three major domains: micronutrients (vitamins and minerals), macronutrients (proteins, peptide-based supplements, and omega-3 long-chain polyunsaturated fatty acids, hereafter LC n-3 PUFAs), and nutraceuticals (polyphenols, microbiome-targeted approaches, and functional foods/botanicals). Evidence is appraised according to study quality, effect size, and safety, with priority given to RCTs, meta-analyses, and large prospective studies reporting skeletal outcomes. The key message is that supplements cannot replace guideline-based care. Their role is adjunctive and should be tailored to the individual, guided by dietary assessment, laboratory and imaging results, comorbidities, concomitant medications, and the best available evidence.
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Table 2. Primary nutrients and nutraceuticals with varying levels of evidence supporting their specific clinical use in promoting bone health.
Legend: Ca = Calcium; Vit D3 = Vitamin D3 (cholecalciferol); BMD = Bone Mineral Density; PTH = Parathyroid Hormone; RCT = Randomized Controlled Trial; MK-7 = Menaquinone-7 (vitamin K2 subtype); VKA = Vitamin K antagonist; CKD = Chronic Kidney Disease; K-sparing drugs = Potassium-sparing diuretics; EPA = Eicosapentaenoic Acid; DHA = Docosahexaenoic Acid; EGCG = Epigallocatechin gallate ( green tea catechin); FN = Femoral Neck.
Matteo Acanfora, Fanny Valsecchi, Alberto Vassallo. Nutrients, Nutraceuticals, and Bone. Authorea. September 02, 2025., DOI: 10.22541/au.175683894.43461238/v1
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