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invited review • Arch. Endocrinol. Metab. 70 (spe 1) • 2026 • https://doi.org/10.20945/2359-4292-2025-0374 linkcopy

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10.20945/2359-4292-2026-0026

Supplements for bone health

Authorship SCIMAGO INSTITUTIONS RANKINGS

Bonehealth is influenced by a dynamic interplay of genetic, hormonal, and environmental factors, with nutrition playing a vital role throughout life. This review consolidates the current evidence on the roles of essential micronutrients, specifically calcium, vitamin D, vitamin K, magnesium, and phosphorus, in skeletal metabolism and integrity. Calcium and vitamin D, the most extensively studied, have been shown to reduce bone loss and fracture risk, particularly in institutionalized individuals or those with deficiencies, while evidence is less consistent in the general population. Although vitamin K, magnesium, and phosphorus are important for bone physiology, the clinical evidence supporting their supplementation is either limited or context dependent. Additionally, this review explores the current status of micronutrient intake in Brazil and discusses potential risks associated with excessive or inappropriate supplementation, such as cardiovascular issues and mineral metabolism disturbances. An individualized, evidence-informed approach may be beneficial in optimizing bone health while minimizing adverse effects.

Keywords:
Bone health; supplementation; vitamin D; vitamin K; magnesium; phosphorus

Age	AI	EAR	RDA	UL
Infancy to adolescence
0-6 months	200	-	-	1000
6-12 months	260	-	-	1500
1-3 years		500	700	2500
4-8 years		800	1000	2500
9-18 years		1100	1300	3000
Women
19-50 years		800	1000	2500
Post-menopause (51+ years)		1000	1200	2000
During pregnancy/lactation (14-18 years)		1100	1300	3000
During pregnancy/lactation (19-50 years)		800	1000	2500
Men
19-70 years		800	1000	2500
≥ 70 years		1000	1200	2000

Category	Food	Calcium (mg/100g)
Dairy products	Parmesan cheese	1050
	Mozzarella cheese	774.55
	Minas cheese (Brazilian fresh cheese)	1020
	Whole milk powder	887.53
	Whole UHT milk	107.74
	Skimmed UHT milk	134.61
	Whole plain yogurt	207.04
Fish/eggs	Canned sardines in oil	393.37
	Cooked salmon	28.76
	Boiled chicken egg	43.72
Vegetables	Raw collard greens	208.43
	Cooked spinach	66.74
	Cooked broccoli	56.83
	Raw watercress	129.77
	Raw arugula	107.28
Legumes	Cooked carioca beans	106.24
	Cooked soybeans	70.81
	Cooked lentils	19
Nuts/seeds	Raw almonds	269
	Raw sesame seeds	825.45
	Raw Brazil nuts	162.63
Processed soy	Tofu	80.76
Cereals/grains	Enriched wheat flour	16.03
	Sliced bread	129.22
	Rolled oats	49.81
Fruits	Banana	221.99
	Orange	29.93
	Strawberry	15.40

Formulation	Elemental Ca (%)	Recommended Use/Dose	Advantages	Potential Limitations/ Adverse Effects
Calcium carbonate	40	Typically 500-600 mg/day, with meals	High elemental calcium content; widely available; cost-effective	Gastrointestinal intolerance; reduced absorption in achlorhydria, atrophic gastritis, or bariatric surgery; may increase kidney stone risk
Calcium citrate	24.1	500-600 mg/day; can be taken with or without food	Well absorbed regardless of food or gastric acidity; safer in achlorhydria or post-gastric surgery	Slightly lower elemental calcium content
Calcium citrate malate	23	500-600 mg/day	Higher bioavailability; reduced GI side effects; minimal interaction with other nutrients; preserves absorption of zinc, magnesium; lower nephrolithiasis risk	Less widely available; moderate elemental calcium
Tricalcium phosphate	37.5	500-600 mg/day; useful for elderly with low dietary phosphorus or intolerance to carbonate/citrate	Moderate elemental calcium; phosphate supplementation	Contraindicated in hyperphosphatemia, chronic kidney disease, or hypoparathyroidism

Study Type/ Population	Intervention/ Comparison	Main Findings	Conclusions/Observations	References
Patients with CKD	Calcium supplements	Increased arterial calcification	Suggests potential cardiovascular risk; prompted investigation in other populations	(⁴⁹,⁵⁰)
Randomized placebo-controlled trial (women)	Calcium vs placebo	Higher incidence of MI in the calcium group	Secondary analysis; calcium group had more baseline risk factors (smoking, dyslipidemia, hypertension)	(⁵¹)
Meta-analysis (15 trials)	Calcium without vitamin D	Higher relative risk of MI	Indicated increased cardiovascular risk, particularly for MI	(⁵²)
Women’s Health Initiative calcium and vitamin D trial	Initiation of supplementation during follow-up	Increased MI risk, independent of dose (< 500 mg/day or ≥ 1000 mg/day)	Adverse effect not dose-dependent	(⁵³)
Swedish cohort (median follow-up: 19 years)	Dietary and supplemental calcium intake	Nonlinear association between calcium intake and mortality: increased risk with < 600 mg/day and ≥ 1400 mg/day	Higher mortality from ischemic heart disease; greatest risk in women with high dietary intake plus supplements; no association with stroke	(⁵⁴)
Prospective cohort (n = 23,980; mean follow-up: 11 years)	Calcium supplements alone	Increased MI risk	Risk highest among users taking calcium without other micronutrients	(⁵⁵)
Subanalysis of RCT (elderly women)	1200 mg/day calcium vs placebo	No significant difference in CV events or MI	Suggests no increased cardiovascular risk at this dosage	(⁵⁶)
Pooled analysis (older adults)	Calcium + vitamin D vs vitamin D alone	Reduced mortality with combined supplementation	Protective effect observed only with calcium + vitamin D	(⁵⁷)
Critical review of major meta-analyses	Various RCTs	Significant methodological limitations	Trials not designed for CV endpoints; inconsistent dosage, duration, and co-administration with vitamin D	(⁵⁸)
Observational studies	Dietary vs supplemental calcium	Dietary calcium not associated with increased CV risk; supplemental calcium potentially harmful	Adverse cardiovascular effects appear confined to supplemental forms	(⁵⁵,⁵⁹,⁶⁰) (⁶¹)
Clinical guideline (NOF & ASPC, 2016)	Dietary and supplemental calcium (with/without vitamin D)	No significant increase in CV, cerebrovascular, or mortality risk up to 2000 mg/day	Recommended intake ≤2000 mg/day, consistent with IOM/NAM	(¹⁰,⁶²)
Meta-analysis (2021; 13 RCTs)	Dietary calcium 700-1000 mg/day or 1000 mg/day supplement	An increased risk of cardiovascular and coronary disease by 15% in healthy postmenopausal women.	Reinforces concerns about excessive supplementation	(⁶³)
American College of Cardiology (2021)	Proposed mechanisms	Transient serum calcium elevations may activate coagulation, enhance smooth muscle contractility, and promote vascular calcification	Mechanistic rationale for accelerated atherosclerosis	(⁶⁴)
UK prospective cohort (n = 434,374)	Habitual calcium supplement use	Higher incidence of CV events and mortality among diabetics; no association in non-diabetics	Diabetes-related insulin resistance and calcium dysregulation may increase susceptibility to CV outcomes	(⁶⁵)

VDR modification	Target cell type	Bone outcomes
Deletion	Osteoblast precursors	No changes in serum markers (calcium, PTH, phosphate, 1,25(OH)₂D) or trabecular bone mass
Deletion	Immature osteoblasts	Increased trabecular bone mass due to reduced RANKL production
Deletion	Mature osteoblasts and osteocytes	No differences in trabecular or cortical bone mass compared to the control group
Overexpression	Mature osteoblasts	Increased cortical and trabecular bone mass
Deletion	Osteoclast precursors	No changes in bone metabolism

Age group or condition	Recommended daily intake	Tolerable upper intake level
1-3 years	600 IU	2500 IU
4-8 years	600 IU	3000 IU
9-70 years	600 IU	4000 IU
>70 years	800 IU	4000 IU
Pregnant and lactating women	600 IU	4000 IU

Food	Serving size	Vitamin D content
Sun-dried mushrooms	100 g	1600 IU ergocalciferol
Fresh mushrooms	100 g	100 IU ergocalciferol
Cod liver oil	1 Tablespoon	1360 IU cholecalciferol
Wild salmon	100 g	600-1000 IU cholecalciferol
Farmed salmon	100 g	100-250 IU cholecalciferol
Canned sardines	100 g	300 IU cholecalciferol
Canned tuna	100 g	230 IU cholecalciferol
Egg yolk	1 Unit	20 IU cholecalciferol
Cooked beef liver	100 g	15 IU cholecalciferol

Intervention	Mechanism of action	Dose	Onset of action	Duration of effect	Comments
0.9% Sodium chloride	Corrects hypovolemia (primary treatment goal). Increases urinary calcium excretion	4-6 L/day (200-300 mL/hour)	Hours	During infusion	Caution in elderly patients and/or those with acute kidney injury and/or heart failure
Loop diuretics	Increases urinary calcium excretion	40-160 mg/day	Hours	During treatment	Initiate only after correction of hypovolemia. Early use may worsen hypercalcemia
Glucocorticoids	Decrease intestinal calcium absorption; reduce 1,25(OH)₂D production; activate 24-hydroxylase	Prednisone (1 mg/kg/day)	2-5 days	Days to weeks	Side effects include hyperglycemia, immunosuppression, and myopathy
Bisphosphonates	Inhibit bone resorption	Pamidronate (90 mg + 0.9% saline 250 mL); Zoledronic acid (4 mg infusion)	24-72 hours	2-4 weeks	Contraindicated in patients with a glomerular filtration rate < 35 mL/min/1.73 m²

MK subtypes	Characteristics
MK-4	Short-chain MK; shorter half-life; main form of vitamin K in the human body; can be produced from vitamin K1; not produced by human gut flora
MK-7	Long-chain MK; longer half-life; found in natto (fermented soy beans), chicken, pork, beef and cheese

Variable	Effects
Coenzyme for the GGCX	Suppresses bone resorption Increases osteoblast genesis
Gla osteocalcin formation	Regulates osteoclast formation Enhances osteoblast collagen accumulation
Gla-rich protein and periostin production	Decreases RANKL expression Increases osteoprotegerin expression
MGP maintains bone metabolism	Induces osteoclast apoptosis SXR signaling induces osteoblast differentiation

	Dosages	Effects on BMD
Philoquinone (K1)	30 mcg - 10 mg	Increase in BMD, decrease in ucOC when used with calcium
Menatetrenone (MK-4)	1,5 mg - 90 mg	Increase in BMD in osteoporotic patients; reduced overall fracture risk
Menaquinone-7 (MK-7)	100 mcg - 10 mg	Increase in BMD in osteoporotic patients; reduced overall fracture risk

Age	mg/day
0 to 6 months	30	AI
7 to 12 months	75	AI
1 to 3 years	65	EAR
	80	RDA
	65	UL of supplementary magnesium
4 to 8 years	110	EAR
	130	RDA
	110	UL of supplementary magnesium
9 to 13 years	200	EAR
9 to 13 years	240	RDA
Male
14 to 18 years	340	EAR RDA
14 to 18 years	410	EAR RDA
19 to 30 years	330	EAR RDA
19 to 30 years	400	EAR RDA
≥ 31 years	350	EAR RDA
≥ 31 years	420	EAR RDA
Female
14 to 18 years	300	EAR RDA
14 to 18 years	360	EAR RDA
19 to 30 years	255	EAR RDA
19 to 30 years	310	EAR RDA
≥ 31 years	265	EAR RDA
≥ 31 years	320	EAR RDA
> 8 years	350	UL of supplementary magnesium

Some examples of foods rich in magnesium	Approximate magnesium content (mg)
Spinach, cooked, 200 g	150
Pasta, whole grain, boiled, 200 g	90
Seeds (pumpkin seeds, sunflower seeds, and/or pine nuts), one tablespoon	55
Mixed nuts, one handful	55
Peanuts, one handful	55
Red kidney beans, boiled, 100 g	50
Banana, a middle-sized	40
Bread, whole grain, one slice	25

			Mean observed intake
Pinheiro and cols.	With history of fragility fracture	Men	244
	With history of fragility fracture	Women	196
	Without history of fragility fracture	Men	201
	Without history of fragility fracture	Women	189
Hermes Sales and cols.	Men	Years old
		14-18	225.2
		19-30	256.8
		31-50	249.4
		51-70	239.1
		≥ 71	237.1
	Women	14-18	199.2
		19-30	196.4
		31-50	193.7
		51-70	188.3
		≥ 71	184.0
Verly-Jr and cols.	2008-2009
	Men	Adolescents	285.8
		Adults	310.0
		Elderly	285.3
	Women	Adolescents	244.3
		Adults	240.8
		Elderly	232.4
	2017-2018
	Men	Adolescents	273.3
		Adults	304.7
		Elderly	275.7
	Women	Adolescents	229.7
		Adults	232.8
		Elderly	225.5
Rodrigues and cols.	Adolescents		243.91

Fractional excretion of phosphate	FEPi (%) = [(Pi_u × Cr_p) / (Pi_p × Cr_u)] × 100
Tubular reabsorption of phosphate (TRPi)	TRP = 1 - FEPi
Tubular maximum reabsorption rate per GFR (TmPi/GFR)	If TRP < 0.86: TmP/GFR = TRP × Pi_p If TRP > 0.86: TmPi/GFR = α × Pi_p α = 0.3 × TRP / (1 - [0.8 × TRP])

Sex and age	Usual phosphorus intake	EAR	RDA	UL
Men
1-3	1030 ± 26.3	380	460	3000
4-8	1145 ± 27.4	405	500	3000
9-13	1321 ± 35.4	1055	1250	4000
14-18	1681 ± 61.5	1055	1250	4000
19-30	1656 ± 53.4	580	700	4000
31-50	1727 ± 25.0	580	700	4000
51-70	1492 ± 30.0	580	700	4000
≥ 71	1270 ± 27.6	580	700	3000
Women
1-3	1030 ± 26.3	380	460	3000
4-8	1145 ± 27.4	405	500	3000
9-13	1176 ± 57.5	1055	1250	4000
14-18	1067 ± 29.8	1055	1250	4000
19-30	1120 ± 40.8	580	700	4000
31-50	1197 ± 25.0	580	700	4000
51-70	1106 ± 34.0	580	700	4000
≥ 71	985 ± 28.8	580	700	3000

Category	Examples/Main foods	Bioavailability/Chemical form	Evidence and potential health risks
Unprocessed and minimally processed foods	Milk, yogurt, white cheese, eggs, fresh meat, fish	Organic phosphate bound to proteins; moderate bioavailability (approximately 40-60 %)	Adequate intake balanced with calcium maintains bone and mineral homeostasis.
Plant sources (legumes, nuts and whole grains)	Beans, lentils, soybeans, peanuts, cashews, oats, whole wheat, brown rice	Organic phosphate in phytates; low bioavailability (< 40%)	High plant intake rarely causes excess phosphorus (P); lower absorption than animal sources.
Processed meats and sausages	Ham, sausage, mortadella, nuggets, industrial hamburgers	Inorganic phosphate additives; high bioavailability (approximately 80-100%)	Major contributors to excessive phosphorus intake; inorganic additives are rapidly absorbed and stimulate FGF-23 secretion, bone remodeling, and vascular calcification.
Cola-type soft drinks & phosphoric acid beverages	Cola, energy drinks, industrial soft drinks	Inorganic phosphate additives; high bioavailability (approximately 80-100%)	Observational data show lower bone mineral density in women with frequent cola intake, although findings were inconsistent across populations.
Ultra-processed foods	Sliced bread, processed cheese, condensed milk, fast food, frozen meals	Mix of highly bioavailable phosphate additives	Primary dietary source of inorganic phosphate additives. Highly absorbable phosphorus increases serum phosphate, PTH, and FGF-23. Chronic intake promotes endothelial dysfunction, vascular calcification, and bone remodeling alterations.

Age (years)	Males			Females
Age (years)	mmol/L	mg/dL		mmol/L	mg/dL
1-4	1.39-1.74	4.3-5.4		1.39-1.74	4.3-5.4
5-13	1.19-1.74	3.7-5.4		1.29-1.68	4.0-5.2
14-15	1.13-1.52	3.5-5.3		1.13-1.58	3.5-4.9
16-17	1.0-1.52	3.1-4.7		1.0-1.52	3.1-4.7
≥18	0.81-1.45	2.5-4.5		0.81-1.45	2.5-4.5

Chronic Hypophosphatemia
Clinical Disorder	Pathophysiological Mechanism
Primary or secondary hyperparathyroidism	Reduced TmPi (tubular maximum phosphate reabsorption); elevated PTH
Phosphorus deficiency or use of phosphate binders	Reduced dietary intake and bioavailability
X-linked hypophosphatemic rickets/osteomalacia (PHEX mutation)	Reduced TmPi; elevated FGF-23
Tumor-induced osteomalacia (FGF-23-producing tumor)
Autosomal dominant hypophosphatemic rickets/ osteomalacia (FGF-23 mutation)
Autosomal recessive hypophosphatemic rickets/ osteomalacia (DMP1 mutation, ENPP1 mutation)
Intravenous iron administration
Fibrous dysplasia/McCune-Albright syndrome (GNAS1 gain of function)
Hypercalciuric hypophosphatemic nephrolithiasis	Reduced TmPi; decreased NaPi2a and NHERF1 expression
Hyperphosphatemia
Clinical Disorder	Pathophysiological Mechanism
Chronic kidney disease	Decreased glomerular filtration rate (GFR); phosphate retention
Hypoparathyroidism	Decreased PTH; increased TmPi
Familial hyperphosphatemic tumoral calcinosis	Genetic mutations in FGF-23, Klotho, or Galnt3
Rhabdomyolysis	Extensive muscle injury with massive phosphate release

Nutrient	Strength of Evidence	Clinical Recommendations	Adverse Effects/Risks
Calcium	High (multiple meta-analyses and RCTs)	Supplementation recommended for individuals with low intake or osteoporosis risk, preferably in combination with vitamin D	Gastrointestinal discomfort, hypercalcemia, nephrolithiasis, possible increased cardiovascular risk in those with adequate dietary intake
Vitamin D	High (consistent RCTs and meta-analyses)	Combined calcium + vitamin D supplementation reduces fracture risk in older adults and deficient populations; monitoring advised in high-dose regimens	Hypercalcemia, hypercalciuria, toxicity with inappropriate use
Vitamin K	Moderate to low (heterogeneous clinical trials)	Evidence suggests potential skeletal benefits, but current data are inconsistent; further RCTs required before recommending routine supplementation	Generally safe; possible interaction with some anticoagulants (e.g., warfarin)
Magnesium	Moderate to low (observational and limited interventional studies)	Maintain adequate dietary intake; supplementation may be beneficial in individuals with low intake or deficiency	Diarrhea, gastrointestinal discomfort; toxicity rare, usually in renal impairment
Phosphorus	Moderate to low (strong physiological rationale; limited clinical data)	Deficiency is uncommon; supplementation reserved for specific conditions (e.g., hypophosphatemia). Excess intake from processed foods should be avoided	Hyperphosphatemia, vascular calcification, secondary hyperparathyroidism, especially in renal disease

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