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Bones

Everything in the library studied for it, medical and holistic together. Within each kind, what was shown to help comes first, strongest evidence first. What was tested and not shown to help stays on the list.

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Medication13 Hormone therapy4 Peptides and SARMs1 Supplements10 Daily life1 Food and drink1 Lab markers12

Medication

BisphosphonatesStrongStudied in women

Fractures in postmenopausal women with osteoporosis

Shown to cut fractures in postmenopausal women with osteoporosis, with clinical spine fractures about 55% lower on alendronate, or 2.7 fewer per 100 women.

Compared with placebo or no treatment [1]; placebo [2][3][4]; placebo and other osteoporosis drugs [5]

The numbers and sources

Effect: In higher-risk women, alendronate lowered clinical vertebral fractures (RR 0.45, 95% CI 0.28 to 0.73, 2.7% fewer), non-vertebral fractures (RR 0.80, 2.8% fewer), hip fractures (RR 0.49, 1.0% fewer) and wrist fractures (RR 0.54, 1.8% fewer) [1]. Risedronate 5 mg a day lowered non-vertebral fractures (RR 0.80, 95% CI 0.72 to 0.90, 2% fewer) and hip fractures (RR 0.73, 1% fewer) [2]. Yearly zoledronic acid lowered spine fractures seen on x-ray from 10.9% to 3.3% over 3 years (RR 0.30, 95% CI 0.24 to 0.38) and hip fractures from 2.5% to 1.4% (HR 0.59), with 25% fewer non-vertebral fractures [3]. Daily and intermittent ibandronate lowered new spine fractures by 62% and 50% [4]. In a network meta-analysis, alendronate, risedronate and zoledronate each lowered hip, spine and non-vertebral fractures, while ibandronate lowered spine fractures only, with lower efficacy [5].
Population: 7,375 higher-risk women in 20 alendronate trials of 1 to 3 years [1]; 14,354 higher-risk women in 9 risedronate trials [2]; 7,765 women, mean age 73 [3]; 2,946 women [4]; 193,987 postmenopausal women in 107 trials [5].
Sources: [1], [2], [3], [4], [5]
Caveats: Many trials in [1] and [2] had unclear or high risk of bias, and most certainty ratings were low to moderate. Risedronate's effect on clinical spine fractures could not be estimated because no events were reported [2].

BisphosphonatesStrong

Bone density in people taking steroid tablets

Shown to raise spine bone density more than placebo or calcium and vitamin D in people on steroid tablets, though less than teriparatide. Trials were too small to judge fractures.

Compared with placebo or calcium and vitamin D [10]; teriparatide and denosumab [10][11]

The numbers and sources

Effect: Every osteoporosis drug raised lumbar spine bone density more than placebo or calcium and vitamin D. Teriparatide raised it more than alendronate (effect size 3.8), risedronate (4.0) and zoledronate (2.4), and zoledronate and denosumab more than oral bisphosphonates [10]. A second network meta-analysis found alendronate, risedronate, etidronate and zoledronate all raised bone density, with teriparatide and denosumab ahead at the spine and femoral neck [11].
Population: 5,260 adults on oral glucocorticoids in 31 studies, 72.5% women [10]; 2,877 patients in 11 trials [11].
Sources: [10], [11]
Caveats: Bone density is a stand-in for fractures, and the included studies were underpowered for fractures [10].

GnRH drugs for fibroidsStrongStudied in women

Add-back hormones and bone during GnRH treatment

Shown to cut spine bone loss from about 5 to 6% to about 1 to 1.5% over a year when estrogen and progestin add-back accompanied elagolix or leuprolide.

Compared with the same GnRH drug without add-back [7][9][10][12]

The numbers and sources

Effect: After 12 months, lumbar spine bone density fell 4.8% on elagolix alone and 1.5% on elagolix with add-back (difference -3.3, 95% CI -4.1 to -2.5) [9]. More women lost bone density on elagolix alone than with estradiol and norethindrone acetate [7]. On leuprolide alone, spine density fell 3.2% at 24 weeks and 6.3% at 52 weeks, against 0.3% and 1.0% with norethindrone acetate 5 mg a day [10]. With GnRH agonists for fibroids, tibolone (SMD 0.36, 3 studies), raloxifene (SMD 1.01, 1 study) and estriol and ipriflavone (single studies) limited bone loss, while tibolone was linked to larger uterine volume and more bleeding [12].
Population: Women with fibroids in elagolix trials [7][9]; women with endometriosis in the leuprolide add-back trials, 29 to 115 per arm [10]; 622 women with fibroids in 12 add-back trials [12].
Sources: [9], [7], [10], [12]
Caveats: The leuprolide add-back data come from endometriosis trials, and the Lupron Depot label states it is not indicated with norethindrone acetate add-back for fibroid anemia [10]. Add-back trials followed women for up to 6 months, too short to measure fractures [12].

BisphosphonatesModerateStudied in women

Fractures in lower-risk women and women with osteopenia

Shown to lower spine and other fractures in lower-risk postmenopausal women, with 15 women with osteopenia treated with zoledronate for 6 years per fracture prevented.

Compared with placebo or no treatment [1]; placebo [2][6]

The numbers and sources

Effect: In lower-risk women, alendronate lowered clinical vertebral fractures (RR 0.45, 95% CI 0.25 to 0.84, 1.4% fewer) and non-vertebral fractures (RR 0.83, 1.6% fewer), with no clear difference in hip fractures (RR 0.76, 95% CI 0.43 to 1.32) or wrist fractures [1]. For risedronate in lower-risk women, effects on fractures were uncertain [2]. In women aged 65 or older with osteopenia, a fragility fracture occurred in 122 on zoledronate and 190 on placebo over 6 years (HR 0.63, 95% CI 0.50 to 0.79), a number needed to treat of 15 [6].
Population: 10,057 lower-risk women in 16 alendronate trials of 1 to 5 years [1]; 989 women in 4 risedronate trials [2]; 2,000 women aged 65 or older with osteopenia, median 10-year hip fracture risk 2.3% [6].
Sources: [1], [2], [6]
Caveats: Low-certainty evidence in [1]. The osteopenia result rests on one trial [6].

BisphosphonatesModerateVery common

Paget's disease of bone

Shown to relieve bone pain in Paget's disease more often than placebo, 31% against 9%, with one zoledronic acid infusion normalizing alkaline phosphatase in 89% at 6 months.

Compared with placebo and other bisphosphonates [12]; risedronate [13]

The numbers and sources

How common: Very common: more than 1 in 10 people.
Effect: Bone pain disappeared in 31% on a bisphosphonate and 9% on placebo (RR 3.42, 95% CI 1.31 to 8.90), a number needed to treat of 5. Fractures did not clearly differ. Zoledronate relieved pain more often than pamidronate or risedronate in single trials [12]. In two 6-month trials, one 5 mg infusion of zoledronic acid normalized serum alkaline phosphatase in 89% against 58% on risedronate 30 mg daily for 2 months, and a therapeutic response was seen in 96% against 74% [13].
Population: 3,168 people in 20 trials, mean age 66 to 74, 51% to 74% men, mostly with raised alkaline phosphatase [12]; 349 adults with moderate to severe Paget's disease, mean age 70 [13].
Sources: [12], [13]
Caveats: Moderate-quality evidence for pain, and mean follow-up was 6 months [12]. Treating to normalize alkaline phosphatase did not improve pain or quality of life over treating symptoms [12].

Thiazide diureticsModerate

Fractures

Linked to about 14% fewer fractures in cohort studies. In one randomized trial, chlorthalidone brought fewer hip and pelvic fractures than amlodipine or lisinopril.

The numbers and sources

Effect: In 11 cohort studies, thiazide users had fewer fractures of any kind than non-users (RR 0.86, 95% CI 0.80 to 0.93) and fewer hip fractures (RR 0.82). The effect was weaker in the higher-quality studies [15]. In a secondary analysis of ALLHAT, people randomized to chlorthalidone had fewer hip and pelvic fractures during the trial than those on amlodipine or lisinopril (HR 0.79, 95% CI 0.63 to 0.98). Over the trial plus later follow-up the difference was not significant (HR 0.87, 95% CI 0.74 to 1.03) [16].
Population: 2,193,160 participants in 11 cohort studies [15]; 22,180 ALLHAT participants with a mean age of 70.4, followed up to 8 years in the trial [16].
Sources: [15], [16]
Caveats: The cohort studies are observational. The randomized evidence is a secondary analysis against other drugs, not placebo [16].

BisphosphonatesLimited

New fractures and survival after a hip fracture

One trial found yearly zoledronic acid after hip fracture surgery lowered new fractures, 8.6% against 13.9%, and deaths, 9.6% against 13.3%, over about 2 years.

Compared with placebo, with calcium and vitamin D in both groups [7]

The numbers and sources

Effect: New clinical fractures occurred in 8.6% on zoledronic acid and 13.9% on placebo, a 35% reduction. New clinical spine fractures were 1.7% against 3.8%, and non-vertebral fractures 7.6% against 10.7%. Deaths from any cause were 9.6% against 13.3%, 28% fewer [7].
Population: 2,127 adults, mean age 74.5, given the first infusion within 90 days of hip fracture repair, median follow-up 1.9 years [7].
Sources: [7]
Caveats: One trial. The pooled analysis of mortality below did not confirm a drop in deaths across trials [8].
Why limited: This rests on one trial, of 2,127 people. Strength counts independent studies that agree, so one trial is limited at any size.

GnRH drugs for fibroidsStrongVery common

Bone density loss

Shown to lower bone density, more over time. With add-back, spine density fell 0.8% to 1.5% at 12 months, and stayed below baseline 12 months after stopping elagolix.

The numbers and sources

How common: Very common: more than 1 in 10 people.
Effect: On Myfembree, lumbar spine density changed -0.23% against +0.18% on placebo at 6 months, and -0.80% at 12 months. A drop of more than 3% at 12 months occurred in 23% on Myfembree and in 17.4% of untreated women with fibroids in an observational cohort. Four women on Myfembree had low-trauma fractures [2]. On Oriahnn, spine density fell 0.7% against 0.1% on placebo at 6 months, and 1.5% at 12 months, with a drop of more than 3% in 27%. Twelve months after stopping, spine density was still 0.72% below baseline, and loss continued in 24%, partly recovered in 46% and fully recovered in 30%. Fractures occurred in 7 of 453 women on Oriahnn (1.5%) and 1 of 196 on placebo (0.5%) [6]. Without add-back, spine density fell 4.8% at 12 months on elagolix [9], 2.7% after 3 months of leuprolide in a fibroid trial, and 6.3% at 52 weeks of leuprolide in endometriosis trials [10]. Pooled trials found more bone loss on elagolix than on placebo [7][8].
Population: 254 women on Myfembree and 256 on placebo, 163 followed to 12 months [2]; 305 women on Oriahnn and 150 on placebo, 175 at 12 months [6]; women in the elagolix, leuprolide and pooled trials [7][8][9][10].
Sources: [2], [6], [9], [10], [7], [8]
Caveats: Both labels state the effect of these losses on long-term bone health and fracture risk in premenopausal women is unknown, and limit use to 24 months [2][6].

Progestins for endometriosis and heavy bleedingModerateStudied in womenHow often is not known

Bone loss with the medroxyprogesterone injection

FDA states, in a boxed warning, that women using the injection may lose significant bone mineral density, more with longer use, and that the loss may not fully reverse.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: On Depo-SubQ Provera 104, spine bone density fell 2.7% (95% CI 2.3 to 3.1) at 1 year and 4.1% (95% CI 3.5 to 4.6) at 2 years, and total hip density 1.7% and 3.5%. After 5 years on the intramuscular injection, spine density was 5.38% lower against 0.43% higher in women using no hormonal contraception, and 2 years after stopping it was still 3.13% lower. In adolescents treated for more than 2 years, hip and femoral neck density had not recovered 5 years after stopping [1]. In 6-month endometriosis trials, bone loss was smaller than with leuprolide and returned to baseline within 12 months of stopping [10][11].
Population: 166 women at 1 year and 106 at 2 years [1]. 33 women on the injection and 105 controls at 5 years, 12 and 60 at 7 years [1]. 274 and 300 women with endometriosis [10][11].
Sources: [1], [10], [11]
Caveats: The label states it is unknown whether use in adolescence lowers peak bone mass or raises later fracture risk [1]. Long-term follow-up groups were small.

BisphosphonatesLimitedStudied in women

Continuing alendronate past 5 years

One trial found women who stopped alendronate after 5 years had the same non-vertebral fracture rate as those who continued, but more clinical spine fractures, 5.3% against 2.4%.

Compared with switching to placebo after 5 years [14]

The numbers and sources

Effect: Over 5 more years, non-vertebral fractures were 19% in women who continued and 18.9% in those who switched to placebo (RR 1.00, 95% CI 0.76 to 1.32). Clinical spine fractures were 2.4% against 5.3% (RR 0.45, 95% CI 0.24 to 0.85), and spine fractures on x-ray did not differ. Hip bone density fell 2.4% more after stopping [14].
Population: 1,099 postmenopausal women who had taken alendronate for a mean 5 years [14].
Sources: [14]
Caveats: Fracture was an exploratory outcome. One trial.

Progestins for endometriosis and heavy bleedingLimitedStudied in womenHow often is not known

Fractures with the medroxyprogesterone injection

Linked to more fractures in two case-control studies of women using the contraceptive injection, with higher odds after longer use.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: One study found higher fracture odds with any use (OR 1.44, 95% CI 1.01 to 2.06) and with more than four years of use (OR 2.16, 95% CI 1.32 to 3.53). The other found higher odds with past use of one or two prescriptions (OR 1.17, 95% CI 1.07 to 1.29) and with current use of 3 to 9 prescriptions (OR 1.36) or 10 or more (OR 1.54, 95% CI 1.33 to 1.78) [16].
Population: Women in 2 case-control studies, within a review of 14 observational studies [16].
Sources: [16]
Caveats: Observational, with no meta-analysis, so women who chose the injection may differ from those who did not [16]. These were contraceptive users, not women with endometriosis.

Progestins for endometriosis and heavy bleedingLimitedStudied in womenVery common

Bone density with dienogest

Mixed results: over 24 weeks, dienogest left spine bone density unchanged in two trials. In 60 women taking it for a year or more after surgery, spine density fell 2.7%.

The numbers and sources

How common: Very common: more than 1 in 10 people.
Effect: Spine bone density changed +0.25% on dienogest and -4.04% on leuprolide over 24 weeks [9]. In 140 women measured in a placebo-controlled trial, dienogest had no effect on bone density at 24 weeks [8]. After surgery for endometriomas, spine density fell 2.2% at 6 months and 2.7% at 1 year on dienogest, femoral neck density fell 2.8% at 1 year, and 45 of 60 women (75%) had a significant fall. Density did not fall further in the second year in 24 women [17].
Population: 252 women [9]. 140 women [8]. 60 women aged about 30 after surgery, treated for a mean of 18.6 months [17].
Sources: [9], [8], [17]
Caveats: The longer study had no control group [17].

BisphosphonatesModerateStudied in men

Fractures in men

Not shown to lower fractures in men over two years of use, because trials recorded too few fractures to tell. A Cochrane review called the effect very uncertain.

Compared with placebo [9]

The numbers and sources

Effect: Hip fractures occurred in 2 of 875 men on a bisphosphonate and 2 of 760 on placebo (RR 0.73, 95% CI 0.06 to 8.51). Symptomatic spine fractures were 5 of 1,021 against 7 of 855 (RR 0.49, 95% CI 0.14 to 1.74), and other fractures 25 of 1,130 against 19 of 913 (RR 0.78, 95% CI 0.42 to 1.45) [9].
Population: 2,548 men aged 50 or older in 7 placebo-controlled bisphosphonate trials, average age 52 to 73 [9].
Sources: [9]
Caveats: Very low certainty evidence, with few events and possible selective reporting [9]. The FDA approvals for men rest on bone density gains, not fracture reduction.

Hormone therapy

Menopausal hormone therapyStrongStudied in women

Bone density

Shown to raise bone density in postmenopausal women, with total hip density up 3.7% over 3 years against almost none on placebo.

The numbers and sources

Effect: In the WHI, total hip bone density rose 3.7% over 3 years on estrogen plus progestin, against 0.14% on placebo [3]. Across 24 RCTs, lumbar bone density improved more on hormone therapy than control (SMD 1.52, 95% CI 1.33 to 1.71), and hip density improved with each regimen studied (SMDs 0.57 to 1.36) [2]. In a network meta-analysis of 16 RCTs, hormone therapy alone and with antiresorptive drugs raised lumbar spine density against control [6].
Population: 1,024 women with bone density measured in the WHI trial [3]; 5,089 women in 24 RCTs [2]; 2,861 postmenopausal women in 16 RCTs [6].
Sources: [3], [2], [6]
Caveats: Bone density is not fracture. Controls in the 24-trial review were not all placebo [2].

DHEAModerate

Bone density

Shown to raise hip bone density in older women, with no similar effect in men in pooled trials. No trial counted fractures.

The numbers and sources

Effect: In women, hip bone density rose more on DHEA than placebo, reported as an SMD of -0.5 for placebo against DHEA (95% CI -0.95 to -0.04). For the trochanter the SMD was -0.55 (95% CI -1.10 to 0.00, p = .05). No similar effect was seen in men [9]. In a 2-year trial, women on DHEA gained density at the ultradistal radius and men at the femoral neck [3]. In elderly men, no effect on bone health was found [2].
Population: Healthy older adults in placebo-controlled RCTs [9]; 144 elderly adults [3]; 1,353 elderly men [2].
Sources: [2], [3], [9]
Caveats: Results differ by sex and site. No sourced trial counted fractures.

Menopausal hormone therapyModerateStudied in women

Fractures

Shown to lower fractures in postmenopausal women, 8.6% against 11.1% on placebo, with fewer hip fractures. Overall benefits and harms showed no net benefit.

The numbers and sources

Effect: In the WHI estrogen plus progestin trial, 8.6% of women on treatment and 11.1% on placebo had a fracture (HR 0.76, 95% CI 0.69 to 0.83). The effect did not differ by age, weight, fall history or baseline bone density [3]. Hip fracture HR was 0.66 (95% CI 0.45 to 0.98), 5 fewer hip fractures per 10,000 person-years [4]. The estrogen-alone trial showed similar results for other outcomes, including fewer hip fractures [5].
Population: 16,608 postmenopausal women aged 50 to 79 with a uterus, followed a mean of 5.6 years [3]; 10,739 women after hysterectomy in the estrogen-alone trial [5].
Sources: [3], [4], [5]
Caveats: Even in women at the highest fracture risk, the global index of benefits and harms showed no net benefit (HR 1.03, 95% CI 0.88 to 1.24) [3]. In a network meta-analysis, fracture events were sparse and often not prespecified outcomes [6].

Testosterone therapyModerateStudied in men

Bone density in men

Shown to raise spine bone density about 3.7% in middle-aged and older men, with no change at the hip. Density is not fracture.

The numbers and sources

Effect: Lumbar spine bone mineral density rose 3.7% (95% CI 1.0 to 6.4) over placebo. Femoral neck density did not differ. Bone resorption markers fell by an SMD of -0.6 (95% CI -1.0 to -0.2) [2].
Population: Middle-aged and older men, 29 RCTs [2].
Sources: [2]
Caveats: Density is not fracture. The one large trial that counted fractures found more of them on testosterone (see Risks) [4].

Peptides and SARMs

MOTS-cGrey marketUntested

Bone health

Not studied in people. In mice with their ovaries removed, MOTS-c reduced bone loss, and in the lab it slowed the formation of bone-resorbing cells.

No study in people. This rests on animal studies, lab studies.

The numbers and sources

Effect: In mice with ovariectomy-induced osteoporosis, MOTS-c treatment reduced bone loss measured by micro-CT. In the lab, it inhibited the formation of osteoclasts, the cells that break down bone, partly through AMPK [15]. A 2023 review reports that MOTS-c promotes the growth, maturation and mineralization of osteoblasts, the cells that build bone, and inhibits osteoclast production [16].
Population: Mice, and bone cells in the lab [15][16].
Sources: [15], [16]
Caveats: Bone loss after ovary removal in mice does not show what happens in people. FDA found no human exposure data for MOTS-c by any route [3].

Supplements

CalciumModerate

Bone mineral density

Shown to raise bone density by 0.7% to 1.8% in people over 50, a gain the authors judged unlikely to meaningfully cut fractures.

The numbers and sources

Effect: Calcium supplements raised bone density by 0.7 to 1.8% at five skeletal sites. The gain at later time points was similar to the gain at one year. Calcium from food raised it by similar amounts at most sites [6]. Hip density was 1.06% higher with calcium plus vitamin D than placebo in postmenopausal women [7]. In postmenopausal women with osteoporosis, calcium plus vitamin D raised pelvic density slightly (SMD 0.20, 95% CI 0.05 to 0.35), with no significant change at the lumbar spine, femoral neck or total hip [2].
Population: 59 RCTs in people over 50, 51 of them of supplements (12,257 people) [6]; 36,282 postmenopausal women aged 50 to 79 [7]; 11 RCTs in women with osteoporosis [2].
Sources: [6], [7], [2]
Caveats: The review authors write that gains of this size are unlikely to lead to a clinically meaningful drop in fractures [6].

Horny goat weedModerate

Bone density after menopause

Shown to keep bone density steady over 2 years in postmenopausal women with low bone density, on a blend with soy isoflavones, while it fell on placebo.

The numbers and sources

Effect: In 100 late postmenopausal women with low bone density, a daily blend of 60 mg icariin, 15 mg daidzein and 3 mg genistein held bone density steady over 24 months. With placebo, lumbar spine density fell 2.4% and femoral neck density 1.8%. The groups differed at the lumbar spine at 12 and 24 months and at the femoral neck at 24 months. Both groups took 300 mg of calcium a day, and endometrial thickness showed no detectable hyperplasia [1]. A meta-analysis of 12 RCTs with 1,017 patients found higher bone density when Epimedium was added to conventional osteoporosis drugs (p = 0.03) or used in place of them (p = 0.009) [2]. In 58 postmenopausal women, 740 mg a day of Epimedium prenylflavonoids for 6 weeks raised the bone formation marker BSAP [3]. A 2025 meta-analysis of 10 RCTs (890 patients with primary osteoporosis) found higher lumbar spine bone density with Epimedium as an add-on or alternative to conventional drugs (SMD 1.15, 95% CI 0.61 to 1.70) [4].
Population: 100 postmenopausal women [1]; patients with osteoporosis in 12 RCTs [2] and 10 RCTs [4]; healthy postmenopausal women [3].
Sources: [1], [2], [3], [4]
Caveats: The blend in [1] also contained soy isoflavones. The trials in [2] and [4] compared Epimedium with conventional drugs, not placebo, and the abstract of [2] gives p-values without effect sizes. Review [4] searched Chinese databases.

CalciumModerate

Fractures

Mixed results: recent reviews found calcium alone did not lower fractures and calcium with vitamin D lowered them only slightly. Older reviews found about 11% to 12% fewer.

The numbers and sources

Effect: Recent meta-analyses found little or no effect, and an older one found fewer fractures. A 2026 meta-analysis of 69 trials (153,902 adults) found calcium alone did not significantly lower the risk of any fracture (RR 0.91, 95% CI 0.81 to 1.01, 11 trials, 9,067 people, moderate certainty). Calcium plus vitamin D lowered it slightly (RR 0.91, 95% CI 0.84 to 0.99, 15 trials, 51,126 people, high certainty), below the authors' threshold for a meaningful absolute effect. Other fracture and fall outcomes showed little to no effect [1]. In postmenopausal women with osteoporosis, calcium plus vitamin D did not lower fracture risk (RR 0.98, 95% CI 0.89 to 1.07, 11 RCTs, 43,869 women) [2]. A 2007 meta-analysis of 17 trials (52,625 people) found 12% fewer fractures with calcium or calcium plus vitamin D (RR 0.88, 95% CI 0.83 to 0.95), 24% fewer where adherence was high [3]. A 2015 review found 11% fewer total fractures (RR 0.89, 95% CI 0.81 to 0.96) and no change in hip fractures (RR 0.95, 95% CI 0.76 to 1.18). In the 4 trials at lowest risk of bias (44,505 people), there was no effect at any site, and the authors found signs of publication bias toward calcium [4]. In community-dwelling adults over 50, calcium did not lower hip fracture (RR 1.53, 95% CI 0.97 to 2.42) or other fractures [5].
Population: Adults not on osteoporosis drugs, 87% living in the community [1]. Postmenopausal women with osteoporosis [2]. Adults aged 50 or older in 17 trials [3], 26 trials [4] and 33 trials with 51,145 people [5].
Sources: [1], [2], [3], [4], [5]
Caveats: The 2015 review found only one trial with a clear fracture reduction, in frail women in residential care with low calcium intake and low vitamin D [4]. Evidence for people in residential care or at high fracture risk was limited in the 2026 review [1].

CollagenLimited

Bone density

Limited evidence: one review found higher bone density, partly with added calcium and vitamin D, while another found the bone studies too limited to conclude.

The numbers and sources

Effect: A 2025 meta-analysis found collagen peptides raised bone mineral density at the femoral neck and spine (I² 80.1%) and improved bone turnover markers (SMD 0.40 to 0.58) [10]. A systematic review of 36 RCTs found limitations in the bone studies that prevent definitive conclusions [4]. In 39 older adults after total hip replacement, 15 g a day of collagen for 14 days did not change bone turnover markers [13].
Population: People in RCTs, some given calcium and vitamin D with collagen [10]; RCTs of type I collagen alone [4]; older adults after hip surgery [13].
Sources: [10], [4], [13]
Caveats: Sources disagree. Heterogeneity for bone density was high, and the meta-analysis pooled collagen alone and with calcium and vitamin D [10]. The abstract does not report fracture results [10].

PotassiumLimited

Bone

Limited evidence: alkaline potassium salts lowered a bone breakdown marker, with bone density unchanged in a review and up 1.7% in one trial. No fracture data.

The numbers and sources

Effect: Sources disagree. A meta-analysis of 14 studies found potassium bicarbonate and citrate lowered urinary calcium and the bone breakdown marker NTX, with no effect on bone density [11]. In one 2-year trial, 60 mEq of potassium citrate a day raised lumbar spine density 1.7% over placebo (95% CI 1.0 to 2.3) [12]. In 5 RCTs of postmenopausal women, potassium citrate lowered urinary NTX at 1 month (MD -4.05 nmol BCE/mmol creatinine, 95% CI -8.05 to -0.05). CTX, P1NP, urinary calcium and parathyroid hormone did not differ from placebo [13].
Population: 14 studies of alkaline potassium salts [11]; 201 healthy adults over 65 without osteoporosis, all given calcium and vitamin D [12]; 401 postmenopausal women [13].
Sources: [11], [12], [13]
Caveats: No fracture outcomes. Potassium chloride, the form in salt substitutes, lowered urinary calcium less than the alkaline salts [11].

Vitamin K2Limited

Fractures

Limited evidence: older Japanese trials found fewer fractures, but a 2019 update found no difference in spine fractures and no significant effect in low-bias trials.

The numbers and sources

Effect: Sources disagree. A 2006 meta-analysis of 7 Japanese MK-4 trials found lower odds of vertebral fractures (OR 0.40, 95% CI 0.25 to 0.65), hip fractures (OR 0.23, 95% CI 0.12 to 0.47) and all nonvertebral fractures (OR 0.19, 95% CI 0.11 to 0.35) [1]. A 2019 update found no difference in vertebral fractures (OR 0.96, 95% CI 0.83 to 1.11). Any clinical fracture was lower (OR 0.72, 95% CI 0.55 to 0.95), but in low-bias trials the difference was not significant (OR 0.76, 95% CI 0.58 to 1.01) [2].
Population: Japanese patients in all 7 fracture trials [1]; postmenopausal or osteoporotic adults in 36 studies [2].
Sources: [1], [2]
Caveats: The 2019 authors write that the integrity of some earlier evidence had been questioned since the 2006 review [2]. Both reviews pooled vitamin K1 and K2 trials for bone density.

Vitamin K2Limited

Bone mineral density

Limited evidence: spine density gains vanished after removing high-bias trials. One 3-year trial found slower bone loss in postmenopausal women.

The numbers and sources

Effect: Pooled lumbar spine density was 1.63% higher at 2 years (95% CI 0.10 to 3.16), but removing high-bias trials made the differences smaller and not significant. The 2019 authors conclude there is no evidence of an effect on bone density in postmenopausal or osteoporotic patients [2]. In one 3-year trial, 180 µg of MK-7 a day slowed the age-related loss of density at the lumbar spine and femoral neck, not the total hip [3].
Population: Postmenopausal or osteoporotic adults [2]; 244 healthy postmenopausal women in the Netherlands [3].
Sources: [2], [3]
Caveats: The MK-7 trial abstract gives no effect sizes [3]. Too few trials in men or other groups for conclusions [2].

CreatineStrong

Bone density

Not shown to change bone density in postmenopausal women or in older adults who exercise.

The numbers and sources

Effect: Bone mineral density did not change overall versus placebo in postmenopausal women [3]. In 20 trials (1,093 older adults, 69% women) of creatine with exercise training, total body bone mineral density did not change (MD 0.009 g/cm², p 0.557) [14].
Population: Postmenopausal women, 7 RCTs, 12 to 104 weeks [3]; older adults in exercise programs [14].
Sources: [3], [14]
Caveats: Each review had few bone trials. Neither found a bone effect.

Vitamin DStrong

Fractures, falls and bone density

Not shown to lower fractures, hip fractures or falls in adults mostly not deficient or at high risk. Calcium with vitamin D had little to no effect.

The numbers and sources

Effect: Across 81 RCTs (53,537 participants), vitamin D had no effect on total fracture (RR 1.00, 95% CI 0.93 to 1.07), hip fracture (RR 1.11, 95% CI 0.97 to 1.26) or falls (RR 0.97, 95% CI 0.93 to 1.02). Results were similar for doses above 800 IU a day, and bone density differences ranged from -0.16% to 0.76% over 1 to 5 years [1]. A 2026 review of 69 trials (153,902 participants) found vitamin D alone did not change the risk of any fracture (RR 1.00, 95% CI 0.95 to 1.06, 36 trials, 92,045 participants, high certainty). Calcium with vitamin D gave RR 0.91 (95% CI 0.84 to 0.99, 15 trials), which the authors rated as little to no effect by absolute risk thresholds. Other fracture and fall outcomes showed little to no effect [2]. In VITAL, 2,000 IU a day for a median 5.3 years did not change total fractures (HR 0.98, 95% CI 0.89 to 1.08), nonvertebral fractures (HR 0.97) or hip fractures (HR 1.01, 95% CI 0.70 to 1.47) [3]. In the Finnish Vitamin D Trial, fractures were more frequent on 1,600 IU a day than placebo (HR 1.52, 95% CI 1.06 to 2.18) and did not differ on 3,200 IU a day (HR 1.07, 95% CI 0.72 to 1.58) over a mean 4.1 years [4]. Fall risk was 55% and fall-injury risk 11% in all three arms over 5 years [5].
Population: Adults in 81 trials [1]; adults not on osteoporosis drugs in 69 trials, 87% community dwelling and 73% not at high risk of fractures or falls [2]; 25,871 US men 50 and older and women 55 and older not selected for deficiency, low bone mass or osteoporosis [3]; 2,495 men 60 and older and women 65 and older in Finland, mean baseline 25-hydroxyvitamin D 75 nmol/L [4][5].
Sources: [1], [2], [3], [4], [5]
Caveats: Most participants were not selected for deficiency or high fracture risk, and evidence for high-risk people and residential care was limited [2]. The higher fracture count at 1,600 IU in the Finnish trial did not appear at 3,200 IU [4]. The bone density figures come from one review [1]. Trials that gave calcium with vitamin D were counted in [1] only where the groups differed by vitamin D alone.

MultivitaminLimited

Fractures

One trial found no drop in total, hip or nonvertebral fractures over 3.6 years in older US adults.

The numbers and sources

Effect: In COSMOS, Centrum Silver for a median 3.6 years did not lower total clinical fractures (aHR 1.09, 95% CI 1.00 to 1.19), hip fractures (aHR 1.06, 95% CI 0.80 to 1.42) or nonvertebral fractures (aHR 1.10, 95% CI 1.00 to 1.20) against placebo. 2,083 fractures occurred in all [10].
Population: 21,442 US women aged 65 and older and men aged 60 and older, not selected for osteoporosis [10].
Sources: [10]
Caveats: Fractures were self-reported. An ancillary analysis of a trial designed for cancer and cardiovascular outcomes.
Why limited: This rests on one trial, of 21,442 people. Strength counts independent studies that agree, so one trial is limited at any size.

Daily life

Strength trainingModerateStudied in women

Bone density

Shown to raise hip bone density by about 1% with lower-body strength training in postmenopausal women in a Cochrane review, without a measured drop in fractures.

Compared with control groups in randomized trials [14]; a home-based low-intensity exercise program [15]

The numbers and sources

Effect: Progressive resistance training for the legs raised femoral neck bone density by 1.03% (95% CI 0.24 to 1.82) against controls. Combination programs raised spine density by 3.22%. Fractures did not differ (OR 0.61, 95% CI 0.23 to 1.64) [14]. In women with low bone mass, 8 months of supervised high-intensity resistance and impact training changed lumbar spine density by 2.9% against -1.2%, and femoral neck density by 0.3% against -1.9% [15].
Population: 4,320 postmenopausal women in 43 trials [14]. 101 postmenopausal women with low bone mass, aged about 65 [15].
Sources: [14], [15]
Caveats: Reporting quality in the trials was low [14]. The fracture analysis was small, and the high-intensity trial was one small study with close supervision [15].

Food and drink

DairyStrong

Hip fracture

Mixed results: milk was not linked to hip fracture overall in pooled cohorts, while yogurt and cheese were linked to 22% to 32% lower hip fracture.

Compared with one fewer glass of milk a day [3]; the lowest consumption category [4][5]

The numbers and sources

Effect: In women, each daily glass of milk was not linked to hip fracture (RR 0.99, 95% CI 0.96 to 1.02). In men the estimate was 0.91 (95% CI 0.81 to 1.01) [3]. In a 2020 review, the highest against the lowest intake was linked to lower hip fracture for yogurt (RR 0.78, 95% CI 0.68 to 0.90) but not milk (RR 0.86, 95% CI 0.73 to 1.02) or cheese (RR 0.85, 95% CI 0.66 to 1.08). Milk was linked to lower hip fracture in US cohorts (RR 0.75, 95% CI 0.65 to 0.87) and not in Scandinavian ones (RR 1.00, 95% CI 0.85 to 1.17) [4]. In a 2018 review of cohorts, yogurt (RR 0.75, 95% CI 0.66 to 0.86) and cheese (RR 0.68, 95% CI 0.61 to 0.77) were linked to lower hip fracture, and milk (RR 0.91, 95% CI 0.74 to 1.12) and total dairy (RR 1.02, 95% CI 0.93 to 1.12) were not [5].
Population: 195,102 women with 3,574 hip fractures and 75,149 men with 195 hip fractures in cohorts [3]. Prospective cohorts [4]. 10 cohort and 8 case-control studies [5].
Sources: [3], [4], [5]
Caveats: Observational. Yogurt eaters may follow other habits that also affect bone [4]. The US link may reflect vitamin D added to milk there, according to the review authors [4]. Calcium supplement trials are on the calcium page.

Lab markers

25-hydroxyvitamin DStrong

Broken bones

Linked to more hip fractures at low levels in cohorts, while pooled trials of vitamin D supplements found no reduction in fractures or falls.

The numbers and sources

Effect: In 15 prospective cohort studies, the lowest category of 25-hydroxyvitamin D had a relative risk of hip fracture of 1.58 against the highest (95% CI 1.41 to 1.77), with risk falling as levels rose up to about 24 ng/mL (60 nmol/L) and flat above that [12]. In 81 randomized trials, vitamin D had no effect on total fracture (RR 1.00, 95% CI 0.93 to 1.07), hip fracture (RR 1.11, 95% CI 0.97 to 1.26) or falls (RR 0.97, 95% CI 0.93 to 1.02), and no clinically relevant effect on bone mineral density [13]. In a trial of 2,000 IU a day, total fractures did not differ from placebo (HR 0.98, 95% CI 0.89 to 1.08), with no difference by starting 25-hydroxyvitamin D level [14].
Population: 51,239 participants with 3,386 hip fractures in 15 cohort studies [12]. 53,537 participants in 81 trials [13]. 25,871 generally healthy US adults followed a median 5.3 years [14].
Sources: [12], [13], [14]
Caveats: The cohort finding is observational. The trial participants were not selected for vitamin D deficiency, low bone mass or osteoporosis [14], so the trials say less about people with very low levels.

Sodium levelStrong

Falls and fractures at low sodium

Linked to about twice the odds of falls and of fractures at low sodium in two meta-analyses of observational studies.

The numbers and sources

Effect: In a meta-analysis of 15 studies, hyponatremia was associated with more falls (OR 2.14, 95% CI 1.71 to 2.67). The odds were already higher when the cut-off for hyponatremia was 135 mmol/L (OR 1.26, 1.23 to 1.29). Hyponatremia was also associated with more fractures, particularly hip fractures (OR 2.00, 1.43 to 2.81) [12]. A second meta-analysis found more fractures with hyponatremia in studies that reported odds ratios (OR 1.99, 95% CI 1.50 to 2.63) and in studies that reported hazard ratios (HR 1.62, 1.28 to 2.05) [13].
Population: 51,879 patients in 15 studies, 2,329 of them hyponatremic [12]. 212,889 participants in 15 observational studies, 12 of them pooled [13].
Sources: [12], [13]
Caveats: Observational. The authors of one review write that it is unclear whether hyponatremia is directly associated with fracture or is a surrogate marker of other causes, and call for studies of fracture risk after hyponatremia is corrected [13].

EstradiolModerate

Fractures in older women and men

Linked to more fractures at low levels: 2.5 times the hip fracture risk in older women with undetectable estradiol, and more fractures in older men below 16 pg/mL.

The numbers and sources

Effect: Among women aged 65 or older, those with undetectable estradiol (below 5 pg/mL) had a relative risk of 2.5 for hip fracture (95% CI 1.4 to 4.6) and 2.5 for vertebral fracture (1.4 to 4.2) against women with detectable levels [8]. In older Swedish men measured by mass spectrometry, each standard deviation lower estradiol had a hazard ratio for fracture of 1.34 (1.22 to 1.49). The relation was nonlinear and strong below 16 pg/mL [9].
Population: 133 women with later hip fracture and 138 with later vertebral fracture, compared with randomly selected women from the same cohort, estrogen users excluded [8]. 2,639 men with a mean age of 75, followed for 3.3 years on average [9].
Sources: [8], [9]
Caveats: Observational. The women's results were adjusted for age and weight only [8]. Many routine assays cannot quantify levels this low [4].

Parathyroid hormone (PTH)Moderate

Vitamin D status

Linked to higher PTH at lower vitamin D: 40% of people with 25-hydroxyvitamin D under 20 ng/mL had PTH above 65 pg/mL in 312,962 paired results.

The numbers and sources

Effect: In paired PTH and 25-hydroxyvitamin D results from one reference laboratory, 40% of people with 25-hydroxyvitamin D below 20 ng/mL and 51% of those below 10 ng/mL had PTH above 65 pg/mL. Median PTH fell smoothly as vitamin D rose, with no level above which it stopped falling, and the relation depended strongly on age [8]. In adults aged 60 to 79, the upper limit of PTH was 64 pg/mL in the whole group and 46 in those with 25-hydroxyvitamin D above 30 nmol/L [5]. With a third-generation assay, taking the reference group only from people with 25-hydroxyvitamin D of 30 ng/mL or above lowered the upper limit by 22.4% [9].
Population: 312,962 paired results measured from July 2010 to June 2011 [8]. 280 adults aged 60 to 79 [5]. 898 adults aged 18 to 89 with normal body mass index and kidney function, 183 of them vitamin D replete [9].
Sources: [8], [5], [9], [7], [6]
Caveats: Cross-sectional. The large series is of people whose doctors ordered both tests, not a reference population. Sources disagree on whether the reference range is to be lowered to account for vitamin D: two studies set upper limits near 46 pg/mL [5][7], and a third concluded the limit stays at 65 [6].

Sex hormone binding globulin (SHBG)Moderate

Fractures in older adults

Linked to more fractures at higher levels in older adults, 18% more for each 1 µg/dL higher SHBG across 16 pooled studies.

The numbers and sources

Effect: In a meta-analysis of 16 observational studies, each 1 µg/dL higher SHBG had a relative risk of fracture of 1.18 (95% CI 1.11 to 1.26), with 1.22 (1.12 to 1.33) in men and 1.15 (1.05 to 1.26) in women. By site it was 1.43 (1.23 to 1.65) for hip fracture and 1.31 (1.12 to 1.54) for vertebral fracture [7]. In women aged 65 or older, SHBG of 1.0 µg/dL (34.7 nmol/L) or higher had a relative risk of 2.0 for hip fracture (1.1 to 3.9) and 2.3 for vertebral fracture (1.2 to 4.4) [8]. In older Swedish men, each standard deviation higher SHBG had a hazard ratio for fracture of 1.41 (1.22 to 1.63) [9].
Population: 16 observational studies of older adults [7]. 133 women with later hip fracture and 138 with later vertebral fracture, compared with randomly selected women from the same cohort [8]. 2,639 men with a mean age of 75 [9].
Sources: [7], [8], [9]
Caveats: Observational. One source prints 1.0 µg/dL as 34.7 nmol/L [8]. SHBG rises with age in men [2], and the meta-analysis authors call for study of the mechanisms behind the link [7].

Thyroid stimulating hormone (TSH)Moderate

Fractures

Linked to more hip and other fractures at TSH below 0.45 mIU/L, most at TSH below 0.10, with no link at raised TSH.

The numbers and sources

Effect: Against a TSH of 0.45 to 4.49 mIU/L, people with TSH below 0.45 mIU/L and normal thyroxine had a hazard ratio of 1.36 for hip fracture (95% CI 1.13 to 1.64) and 1.28 for any fracture (1.06 to 1.53). At TSH below 0.10 mIU/L the hazard ratios were 1.61 for hip fracture (1.21 to 2.15), 1.98 for any fracture (1.41 to 2.78) and 3.57 for spine fracture (1.88 to 6.78). No association was found between TSH of 4.50 to 19.99 mIU/L and fracture [20].
Population: 70,298 adults in 13 prospective cohorts, 762,401 person-years, 2,975 hip fractures [20].
Sources: [20]
Caveats: Observational. The authors state that trials are lacking on whether treating a low TSH prevents fractures [20].

Vitamin A (retinol) levelModerate

Fracture

Linked to more hip fractures at both high and low blood retinol in a meta-analysis of four cohorts, with no link to fractures overall.

The numbers and sources

Effect: In a meta-analysis of prospective studies, both high and low blood retinol went with more hip fractures (RR 1.87, 95% CI 1.31 to 2.65, and RR 1.56, 1.09 to 2.22), in a U-shaped relation. The risk of all fractures taken together did not differ by blood retinol [10]. In one of the cohorts, Swedish men in the highest fifth of serum retinol (above 75.62 µg/dL) had a rate ratio of 1.64 (1.12 to 2.41) for any fracture and 2.47 (1.15 to 5.28) for hip fracture against the middle fifth (62.16 to 67.60 µg/dL). Men above the 99th percentile (103.12 µg/dL) had about seven times the fracture risk of men with lower levels [4].
Population: 8,725 participants in four prospective studies of blood retinol [10]. 2,322 men aged 49 to 51 at enrollment, followed for 30 years, with 266 fractures [4].
Sources: [10], [4]
Caveats: Observational, from four cohorts. The Swedish cohort measured retinol once, at about age 50, in men only [4].

Follicle-stimulating hormone (FSH)LimitedStudied in women

Bone loss across the menopausal transition

One cohort found FSH levels and their change over 4 years predicted spine and hip bone loss through the menopausal transition, while estradiol changes did not.

The numbers and sources

Effect: Over 4 years, lumbar spine bone density fell 5.6% in women who reached natural postmenopause and 3.2% in late perimenopause. Baseline FSH, later FSH and their interaction predicted the loss. With a baseline FSH below 25 mIU/mL, a follow-up FSH above 70 predicted a 4-year spine loss of 0.05 g/cm2. Estradiol below 35 pg/mL went with lower bone density, but yearly estradiol changes did not predict loss [12].
Population: 2,311 premenopausal or early perimenopausal women at five sites of the Study of Women's Health Across the Nation, examined yearly for five visits [12].
Sources: [12]
Caveats: Observational, from one cohort. FSH rises as ovarian function declines, so it may mark the stage of the transition and not act on bone itself.

Total testosteroneLimitedStudied in men

Fractures in a trial that raised testosterone

One trial found more fractures, not fewer, when testosterone was raised in men with low levels: 3.5% against 2.5% on placebo over 3 years.

The numbers and sources

Effect: In a fracture substudy of the same cardiovascular trial, a clinical fracture occurred in 91 of 2,601 men on testosterone gel (3.50%) and 64 of 2,603 on placebo (2.46%), a hazard ratio of 1.43 (95% CI 1.04 to 1.97). Fracture incidence also appeared higher with testosterone for all other fracture end points [24].
Population: 5,204 men aged 45 to 80 with two morning testosterone levels below 300 ng/dL, median follow-up 3.19 years [24].
Sources: [24]
Caveats: A marker that tracks an outcome is not always one whose correction changes it. The authors note that testosterone treatment had improved bone density in earlier studies, and this result ran the other way [24].
Why limited: This rests on one trial, of 5,204 people. Strength counts independent studies that agree, so one trial is limited at any size.

EstradiolModerateStudied in women

Fractures, stroke and breast cancer in trials of estrogen therapy after menopause

Mixed results: in one large trial estrogen alone cut fractures by 27% and raised strokes by 33% in postmenopausal women, with little or no difference in breast cancer.

The numbers and sources

Effect: A Cochrane review drew its main results from the Women's Health Initiative. Among 10,739 women who had had a hysterectomy, oral conjugated equine estrogen for an average of 7 years, against placebo, gave relative risks of 0.73 for all clinical fractures (95% CI 0.65 to 0.80), 1.33 for stroke (1.06 to 1.67), 1.78 for gallbladder disease requiring surgery (1.42 to 2.24), 0.94 for coronary events (0.78 to 1.13), 1.32 for venous clots (1.00 to 1.74) and 0.79 for breast cancer (0.61 to 1.01). Among 16,608 women with a uterus, estrogen with a progestin for 5.6 years gave 0.78 for fractures (0.71 to 0.86), 1.39 for stroke (1.09 to 2.09), 2.03 for venous clots (1.55 to 6.64) and 1.27 for breast cancer (1.03 to 1.56) [10].
Population: 24 randomized trials with 45,660 women, most of them postmenopausal American women with a mean age over 60 [10].
Sources: [10], [7]
Caveats: A marker that tracks an outcome is not always one whose correction changes it. Higher estradiol went with more breast cancer in cohorts [7], and estrogen given alone did not raise it in this trial. The trials set a dose and did not target a blood level. The review's authors caution that the results rest on one study of oral therapy, and that only about 30% of the women were aged 50 to 59 [10].

Calcium levelLimited

Surgery for mildly raised calcium from an overactive parathyroid

One trial found parathyroid surgery did not reduce deaths, fractures, heart events or kidney stones over 10 years in mild primary hyperparathyroidism.

The numbers and sources

Effect: In people with mild primary hyperparathyroidism and modest hypercalcemia, 15 had died 10 years after randomization, 8 assigned to surgery and 7 to observation. Over an extended period to 2018 there were 44 deaths, 24 and 20. Cardiovascular events, cerebrovascular events, cancer, peripheral fractures and kidney stones numbered 52 in the surgery group and 49 in the observation group. Vertebral fractures occurred in 7 patients in each group [7].
Population: 191 patients at 8 Scandinavian centers, 95 assigned to parathyroidectomy and 96 to observation [7].
Sources: [7]
Caveats: One trial of 191 people, and 50 withdrew during the study. It enrolled mild disease without known complications, and the abstract does not report calcium levels after surgery [7].

Parathyroid hormone (PTH)Limited

Death and illness in a trial of surgery for mild primary hyperparathyroidism

One trial found parathyroid surgery for mild primary hyperparathyroidism did not change deaths, fractures or cardiovascular events over 10 years compared with observation.

The numbers and sources

Effect: After 10 years, 8 patients had died in the surgery group and 7 in the observation group. Over the extended follow-up to 2018 there were 24 and 20 deaths. Cardiovascular events, strokes, cancer, peripheral fractures and kidney stones together numbered 52 in the surgery group and 49 in the observation group, and 7 patients in each group had vertebral fractures [15].
Population: 191 patients with mild primary hyperparathyroidism at eight Scandinavian centers, 95 assigned to surgery and 96 to observation [15].
Sources: [15]
Caveats: One trial of 191 people, 50 of whom withdrew. It studied mild disease with modest high calcium and no known complications, so it does not describe more severe disease [15].