Bone Health

Moderate Improvement

Small Improvement

A meta-analysis of 6 RCTs (n=614) found ossein-hydroxyapatite complex (OHC) preserved +1.02% more BMD than calcium carbonate. The largest comparative study (n=851 perimenopausal women, 3 years) showed OHC maintained stable lumbar BMD while calcium carbonate lost 3.1% (p<0.001), despite the OHC group receiving less elemental calcium (712 vs 1000 mg/day). Additional RCTs in postmenopausal, surgically menopausal, and senile osteoporosis populations consistently favor OHC over calcium carbonate for BMD preservation.

Two controlled trials in corticosteroid-treated patients found MCHC attenuated bone loss. Stellon et al. (1985) showed MCHC halted bone mineral content loss in 36 patients with chronic active hepatitis on corticosteroids over 2 years (p<0.025 for cortical thickness). Pines et al. (1984) found MCHC (6-8 g/day) significantly reduced bone pain (p<0.001) and slowed cortical bone loss in 40 patients on long-term prednisolone.

Moderate Improvement

In vitro studies show cajanin (10nM) and medicarpin (6nM) promote osteoblast differentiation and mineralization with potency comparable to or exceeding 17β-estradiol. In ovariectomized rat models of postmenopausal osteoporosis, these compounds preserved bone mineral density and improved bone microarchitecture. Medicarpin acts through non-estrogenic mechanisms, potentially allowing bone benefits without hormonal side effects.

Animal and human studies show that electrolyte balance—particularly calcium, magnesium, and the acid-base effects of potassium bicarbonate—influences urinary mineral excretion and bone mineral retention. Alkaline potassium salts may reduce urinary calcium loss, though direct bone density outcomes from combined electrolyte supplementation are limited.

A 12-week double-blind RCT in 50 elderly participants found longan pulp and seed extract significantly reduced alkaline phosphatase levels versus placebo (mean difference -7.06 U/L, p=0.023), though other bone turnover markers did not reach significance. In vitro studies show longan fruit extract stimulates osteoblast differentiation via Erk1/2-dependent RUNX2 activation.

Phosphorus is essential for hydroxyapatite crystal formation in bone. An RCT found phosphate and carbonate salts of calcium supported robust bone building in osteoporosis. However, adequate calcium co-intake is required; phosphorus supplementation without sufficient calcium may paradoxically impair bone health by stimulating PTH secretion.

Observational studies associate excessive phosphorus intake (particularly phosphoric acid from soft drinks) with lower bone mineral density. The mechanism involves chronic PTH elevation from high phosphorus-to-calcium ratio, leading to increased bone resorption. This effect is most pronounced when calcium intake is inadequate relative to phosphorus.

Population-based epidemiological studies (including Framingham cohort data) link higher dietary silicon intake with better bone mineral density, particularly in premenopausal women. One RCT in osteopenic women showed improvement in bone formation markers with ch-OSA added to calcium/vitamin D supplementation versus calcium/vitamin D alone.

Small Improvement

Small Increase

Small Improvement

Small Improvement

Limited human trials suggest alkali citrate supplementation may modestly reduce bone resorption markers and urinary calcium loss, particularly in postmenopausal women. The mechanism relates to systemic acid-base balance correction rather than direct bone effects, and clinical significance for fracture prevention remains unclear.

A single-blind, randomized, placebo-controlled 96-week trial in 17 healthy young women found that 12 g/day lactosucrose significantly reduced fecal calcium excretion and increased apparent calcium absorption and retention compared to placebo. Magnesium and phosphorus absorption were also improved. Effects were maintained throughout the long treatment period.

In vitro studies show osthole stimulates osteoblast differentiation and bone formation. Animal models of osteoporosis suggest inhibition of osteoclast activity and improved bone density. No human data exists.

In ovariectomized rats (a model of postmenopausal osteoporosis), a dong quai-containing formula (dang-gui-ji-hwang-yeum) improved bone density markers. A review of traditional Chinese medicines also identified dong quai components as having roles in osteogenesis and angiogenesis in preclinical models. No human clinical trial data exists for bone outcomes.

In vitro, scopoletin and scopolin (coumarins isolated from A. iwayomogi) suppressed RANKL-induced osteoclast differentiation in RAW 264.7 macrophage cells by scavenging intracellular ROS and superoxide anions during osteoclastogenesis. Single in vitro study with no animal or human follow-up.

In vitro and animal studies show myricetin induces osteoblast differentiation through the BMP-2/p38 MAPK pathway and may inhibit osteoclast-mediated bone resorption. Preclinical models suggest anti-osteoporotic effects, but no human clinical trials have been conducted.

In ovariectomy-induced osteoporosis models, 7,8-DHF modulated bone formation and resorption and ameliorated bone loss, including via PI3K/AKT/NRF2 pathway in BMSCs. However, one study found 7,8-DHF impaired fracture healing in mice, suggesting context-dependent effects on bone metabolism.

In a rat model, the ratio of n-6 to n-3 essential fatty acids significantly affected calcium balance and bone parameters, with lower n-6/n-3 ratios associated with improved calcium absorption and bone mineral content.

In 75 aged laying hens, dietary supplementation with γ-PGA combined with nanosized zinc oxide increased eggshell thickness and elevated serum mineral concentrations compared to conventional supplementation. Separately, the compound's known calcium-binding properties suggest potential for enhancing calcium absorption, though direct human evidence is lacking.

No effect

No effect

A review of preclinical evidence (PMID:25109459) identifies Salvia miltiorrhiza as a source of compounds with anti-osteoporotic potential in animal models. One clinical study using point injection of red sage root extract reported improved hip joint function in patients with ischemic femoral head necrosis (PMID:19526810). Oral supplementation data in humans is lacking.

A single preclinical study found clove extract rich in eugenol and eugenol derivatives showed bone-preserving efficacy in an animal model of bone loss. The mechanism may involve antioxidant and anti-resorptive properties. No human clinical trials.

One preclinical study reported that cyanidin-3-O-β-D-glucoside improved bone indices. No human evidence or replication studies available.

No effect

No effect

An in vitro study found calcium threonate enhanced mineralized nodule formation and collagenous protein production in cultured cells over 5 weeks. Collagenous proteins accounted for 85% of the increase in total protein. No in vivo confirmation exists.

An in vitro study (Yu 2012) showed D-chiro-inositol, pinitol's active metabolite, dose-dependently inhibited RANKL-induced osteoclast differentiation by downregulating NFATc1 transcription factor. No animal or human studies have examined pinitol directly for bone outcomes.

Rapid and sustained reduction in bone resorption markers (CTX) within days of administration.

Teriparatide rapidly increases bone formation markers (P1NP, osteocalcin) within weeks of treatment initiation.

Romosozumab rapidly increases bone formation markers (P1NP) with peak at 2 weeks, demonstrating its anabolic effect.

Romosozumab reduces bone resorption markers (CTX), demonstrating its unique dual mechanism of action.

Calcitonin reduces bone resorption markers through direct inhibition of osteoclast activity.

Calcitonin is FDA-approved for acute treatment of hypercalcemia, rapidly lowering serum calcium through inhibition of bone resorption.

Calcitonin provides pain relief in osteoporosis and other painful bone conditions through central and peripheral analgesic mechanisms.

Sermorelin induced catch-up growth in GH-deficient children with significant increases in height velocity sustained during 12 months of treatment, with effects maintained for up to 36 months.

In animal studies, ipamorelin dose-dependently increased longitudinal bone growth rate from 42 μm/day to 52 μm/day, with pronounced effects on body weight gain.

12-week treatment with ipamorelin increased total tibial and vertebral bone mineral content in adult rats, primarily through increased bone dimensions rather than volumetric density.

Ipamorelin counteracted glucocorticoid-induced decreases in bone formation, with periosteal bone formation rate increasing four-fold when combined with glucocorticoids.