Condition

Osteoporosis

Osteoporosis is a condition in which bone breakdown outpaces bone building, leaving bones porous and fragile, a shift that speeds up after menopause as estrogen falls. Among supplements, vitamin K and vitamin D have the most support, and trials found bone mineral density improved with each, with the evidence moderate for both. The vitamin D findings came from only two studies and the gain was small, and these trials looked at bone density rather than fractures.

Sources: PMID 31076817; PMID 39640483

Supplements studied: 4
Medicines and peptides: 5
Graded outcomes: 30
Trials: 8
People studied: 62,544

Evidence by supplement

Strong
Moderate
Limited
Very limited

4 supplements

Vitamin K

Vitamin K: outcomes studied for Osteoporosis
Grade	Outcome	Effect	Size	Studies	People
	Bone Mineral Density Moderate Improvement	Improves (the measure goes up)	Moderate effect	18 studies	4,800 people
Studies that measured bone mineral density Effect of vitamin K on bone mineral density: a meta-analysis of randomized controlled trialsJ Bone Miner Metab · PMID 21674202 A longitudinal study of the effect of vitamin K2 on bone mineral density in postmenopausal women a comparative study with vitamin D3 and estrogen-progestin therapyMaturitas · PMID 10227010 Factors affecting bone loss in female endurance athletes: a two-year follow-up studyAm J Sports Med · PMID 14623654 and 15 more on the Vitamin K page
	Weight	Improves (the measure goes down)		2 studies	40 people
Studies that measured weight The effect of vitamin K supplementation on cardiovascular risk factors: a systematic review and meta-analysis.J Nutr Sci · PMID 38282652 Effect of Menaquinone-7 (MK-7) Supplementation on Anthropometric Measurements, Glycemic Indices, and Lipid Profiles: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Prostaglandins Other Lipid Mediat · PMID 40054729
	Estrogen	Changes; see studies		1 study	40 people
Studies that measured estrogen Time-dependent effects of vitamin K2 (menatetrenone) on bone metabolism in postmenopausal womenEndocr J · PMID 12201222
	Fracture Risk	Changes; see studies		1 study	11,112 people
Studies that measured fracture risk Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosisJ Bone Miner Res · PMID 10750566
	Total cholesterol	Improves (the measure goes down)			40 people

Vitamin D

Vitamin D: outcomes studied for Osteoporosis
Grade	Outcome	Effect	Size	Studies	People
	Bone Mineral Density Small Improvement	Improves (the measure goes up)	Small effect	2 studies	5,522 people
Studies that measured bone mineral density Efficacy of combination therapy of vitamin D and bisphosphonates in the treatment of postmenopausal osteoporosis: a systematic review and meta-analysis.Front Pharmacol · PMID 39640483 Changes in bone density and microarchitecture following treatment of Graves' disease and the effects of vitamin D supplementation. A randomized clinical trial.Osteoporos Int · PMID 39264438
	Fracture Risk	Changes; see studies		1 study	42,279 people
Studies that measured fracture risk Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trialsArch Intern Med · PMID 19307517
	Bone-specific Alkaline Phosphatase	Improves (the measure goes up)			8,058 people

Horny Goat Weed

Bone Mineral Density: improves
Circulating Alkaline Phosphatase: improves
Estrogen: changes; see studies

Horny Goat Weed: outcomes studied for Osteoporosis
Grade	Outcome	Effect	Size	Studies	People
	Bone Mineral Density Small Improvement	Improves (the measure goes up)	Small effect	2 studies	956 people
Studies that measured bone mineral density Epimedium-derived phytoestrogen flavonoids exert beneficial effect on preventing bone loss in late postmenopausal women: a 24-month randomized, double-blind and placebo-controlled trialJ Bone Miner Res · PMID 17419678 Epimedium for Osteoporosis Based on Western and Eastern Medicine: An Updated Systematic Review and Meta-Analysis.Front Pharmacol · PMID 35431937
	Circulating Alkaline Phosphatase Small Decrease	Improves (the measure goes down)	Small effect		1,017 people
	Estrogen	Changes; see studies		1 study	267 people
Studies that measured estrogen Bioassays for estrogenic activity: development and validation of estrogen receptor (ERalpha/ERbeta) and breast cancer proliferation bioassays to measure serum estrogenic activity in clinical studiesAssay Drug Dev Technol · PMID 19382890
	Interleukin 6	Improves (the measure goes down)			120 people
	Pain	Improves (the measure goes down)			1,017 people
	Serum Calcium	Improves (the measure goes up)			1,017 people
	Serum Phosphorus	Changes; see studies			147 people

Soy Protein

Bone Mineral Density: improves

Soy Protein: outcomes studied for Osteoporosis
Grade	Outcome	Effect	Size	Studies	People	Studies list
	Bone Mineral Density	Improves (the measure goes up)		1 study	393 people
Studies that measured bone mineral density Animal Versus Plant Protein and Adult Bone Health: A Systematic Review and Meta-Analysis From the National Osteoporosis FoundationPLoS One · PMID 29474360

Prescription medicines and peptides studied, for context

These are not supplements. Most need a prescription, and some are research compounds with no approved use. They are listed so the supplement evidence above can be read against them.

5 medicines and peptides

Denosumab (Prolia/Xgeva)

Vertebral Fracture Risk: improves
Hip Fracture Risk: improves
Nonvertebral Fracture Risk: improves

Denosumab (Prolia/Xgeva): outcomes studied for Osteoporosis
Outcome	Effect	Size	Studies
Vertebral Fracture Risk FREEDOM trial showed 68% reduction in new vertebral fractures (2.3% vs 7.2% placebo, P<0.001) over 3 years in postmenopausal women.	Improves (the measure goes down)	Large effect	32 studies
Hip Fracture Risk FREEDOM trial showed 40% reduction in hip fractures (0.7% vs 1.2% placebo, HR 0.60, P=0.04) over 3 years.	Improves (the measure goes down)	Moderate effect	32 studies
Nonvertebral Fracture Risk FREEDOM trial showed 20% reduction in nonvertebral fractures (6.5% vs 8.0% placebo, HR 0.80, P=0.01) over 3 years.	Improves (the measure goes down)	Moderate effect	32 studies
Lumbar Spine BMD 10-year extension showed 21.7% increase in lumbar spine BMD from baseline, with continued gains without plateau.	Improves (the measure goes up)	Large effect	27 studies
Total Hip BMD 10-year extension showed 9.2% increase in total hip BMD from baseline with sustained improvement.	Improves (the measure goes up)	Large effect	27 studies
Femoral Neck BMD 10-year extension showed 9.0% increase in femoral neck BMD from baseline.	Improves (the measure goes up)	Large effect	27 studies

Teriparatide (Forteo)

Glucocorticoid-Induced Osteoporosis: improves
Vertebral Fracture Risk: improves
Non-Vertebral Fracture Risk: improves

Teriparatide (Forteo): outcomes studied for Osteoporosis
Outcome	Effect	Size	Studies
Glucocorticoid-Induced Osteoporosis Teriparatide is superior to bisphosphonates for glucocorticoid-induced osteoporosis, with greater BMD increases at spine and hip.	Improves (the measure goes up)	Moderate effect	27 studies
Vertebral Fracture Risk Meta-analysis showed 70% reduction in vertebral fracture risk (RR 0.30, 95% CI: 0.21-0.44). TOWER trial showed 80% reduction with cumulative incidence of 3.1% vs 14.5% placebo.	Improves (the measure goes down)	Large effect	22 studies
Non-Vertebral Fracture Risk Meta-analysis showed 38% reduction in non-vertebral fracture risk (RR 0.62, 95% CI: 0.44-0.87) in postmenopausal women with osteoporosis.	Improves (the measure goes down)	Moderate effect	22 studies
Lumbar Spine BMD 24 months of treatment increased lumbar spine BMD by 10.7-13.4%, with 83% of patients showing >3% BMD increase.	Improves (the measure goes up)	Large effect	19 studies
Femoral Neck BMD 24 months of treatment increased femoral neck BMD by 2.7-3.3%, with 40% of patients showing significant response.	Improves (the measure goes up)	Moderate effect	18 studies
Total Hip BMD 24 months of treatment increased total hip BMD by 3.0-3.7% from baseline.	Improves (the measure goes up)	Moderate effect	18 studies

Romosozumab (Evenity)

Clinical Fracture Risk: improves
Vertebral Fracture Risk: improves
Hip Fracture Risk: improves

Romosozumab (Evenity): outcomes studied for Osteoporosis
Outcome	Effect	Size	Studies
Clinical Fracture Risk FRAME trial showed lower risk of clinical fractures (composite of nonvertebral and symptomatic vertebral) with romosozumab vs placebo at 12 months.	Improves (the measure goes down)	Moderate effect	22 studies
Vertebral Fracture Risk FRAME trial showed 73% reduction in new vertebral fractures at 12 months (0.5% vs 1.8% placebo, P<0.001). ARCH showed 48% lower risk vs alendronate at 24 months.	Improves (the measure goes down)	Large effect	21 studies
Hip Fracture Risk ARCH trial showed reduced hip fracture risk with romosozumab-to-alendronate sequence vs alendronate alone.	Improves (the measure goes down)	Moderate effect	21 studies
Total Hip BMD ARCH showed 6.3% increase in total hip BMD at 12 months with romosozumab vs 2.9% with alendronate (P<0.001).	Improves (the measure goes up)	Large effect	15 studies
Lumbar Spine BMD Significant increases in lumbar spine BMD with romosozumab treatment, greater than placebo, alendronate, and teriparatide at 12 months.	Improves (the measure goes up)	Large effect	15 studies
Femoral Neck BMD Substantial gains in femoral neck BMD with romosozumab, contributing to reduced hip fracture risk.	Improves (the measure goes up)	Large effect	15 studies

Abaloparatide

Lumbar Spine BMD: improves
Vertebral Fracture Risk: improves
Non-Vertebral Fracture Risk: improves

Abaloparatide: outcomes studied for Osteoporosis
Outcome	Effect	Size	Studies
Lumbar Spine BMD 8.48% increase at 12 months vs 1.17% placebo in men (ATOM trial)	Improves (the measure goes up)	Large effect	16 studies
Vertebral Fracture Risk ACTIVE trial: 86% reduction in new vertebral fractures vs placebo (P<0.001)	Improves (the measure goes down)	Large effect	14 studies
Non-Vertebral Fracture Risk ACTIVE trial: 43% reduction in non-vertebral fractures vs placebo	Improves (the measure goes down)	Moderate effect	14 studies
Total Hip BMD 2.14% increase vs 0.01% placebo at 12 months	Improves (the measure goes up)	Moderate effect	14 studies
Femoral Neck BMD 2.98% increase vs 0.15% placebo at 12 months	Improves (the measure goes up)	Moderate effect	14 studies

Calcitonin Salmon

Vertebral Fracture Risk: improves
Acute Fracture Pain: improves
Bone Mineral Density: improves

Calcitonin Salmon: outcomes studied for Osteoporosis
Outcome	Effect	Size	Studies
Vertebral Fracture Risk PROOF trial showed 33% reduction in new vertebral fractures with 200 IU nasal spray (RR 0.67, P=0.03) over 5 years. 36% reduction in women with 1-5 prevalent fractures.	Improves (the measure goes down)	Moderate effect	15 studies
Acute Fracture Pain Multiple RCTs demonstrate significant analgesic effect in acute osteoporotic vertebral compression fractures, with reduced pain scores and analgesic requirements.	Improves (the measure goes down)	Moderate effect	15 studies
Bone Mineral Density Calcitonin produces modest increases in lumbar spine BMD, though effects are less pronounced than bisphosphonates or other antiresorptives.	Improves (the measure goes up)	Small effect	16 studies

Key findings

Bone Mineral DensityVitamin KImproves (the measure goes up)
Circulating Alkaline PhosphataseHorny Goat WeedImproves (the measure goes down)

Safety notes in the studies

FRAME trial showed lower risk of clinical fractures (composite of nonvertebral and symptomatic vertebral) with romosozumab vs placebo at 12 months.
Meta-analysis showed 70% reduction in vertebral fracture risk (RR 0.30, 95% CI: 0.21-0.44).
Meta-analysis showed 38% reduction in non-vertebral fracture risk (RR 0.62, 95% CI: 0.44-0.87) in postmenopausal women with osteoporosis.

The Osteoporosis protocol

3 primary supplements · 4 supporting supplements

Vitamin D32,000–4,000 IU daily (target 40–60 ng/mL)
Calcium1,000–1,200 mg daily (from diet + supplements, divided doses)
Vitamin K2 (MK-7)100–200 mcg daily

See the full protocol

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Studies cited

2 studies from PubMed

Short-Term Effects of Kefir-Fermented Milk Consumption on Bone Mineral Density and Bone Metabolism in a Randomized Clinical Trial of Osteoporotic PatientsPLoS One · PMID 26655888
The effect of garlic tablet on pro-inflammatory cytokines in postmenopausal osteoporotic women: a randomized controlled clinical trialJ Diet Suppl · PMID 23039014