Table 2.

Osteogenic Potential of NMCs: Preclinical, Clinical, In Vitro, and In Vivo Studies

Natural medicinal compound	Type of study/biological system	Results	Refs
Ginger	Randomized, double-blinded, placebo-controlled, multicenter, parallel-group, 6-week study/ 261 patients with knee osteoarthritis	63% of patients who were administered ginger extracts found relief compared with the 50% under placebo. The subjects in the ginger group showed improvement in osteoarthritis conditions in terms of standing, walking, and less frequent resorting to acetaminophen.	[72]
	In vivo study/ ovariectomy-induced rat	A crude extract of ginger (26 mg/kg/day) was efficient to preserve the BMD, suggesting prevention of osteoclast activity along with its anti-inflammatory effects.	[73]
Garlic	In vivo study/ ovariectomized rats	Garlic oil supplementation recovered the loss in bone densities found in ovariectomized rats. Significant changes in primary and secondary markers, such as ALP, TRAP, urinary excretion of calcium, phosphate, hydroxyproline, and urinary calcium to creatinine ratio were reported.	[74]
		Garlic oil-supplemented diet suppressed the effect of ovariectomy in rats, such as low BMD, and low tensile strength.	[75]
Turmeric	In vivo study/ insulin-dependent diabetic rat model	Oral administration of curcumin suppressed osteoclast-induced bone resorption.	[76]
	In vitro study/RAW 264.7 cells	Prevented RANKL-induced NF-κβ activation and osteoclastogenesis.	[77]
	In vivo study/ ovariectomized rats	Curcumin administration (15 mg/day) for 6 months increased the size of the femur and resulted in an increase in energy to fracture. Curcumin produces beneficial changes in bone turnover and increases in bone strength.	[78]
Soy isoflavones	Randomized, double-blinded, placebo-controlled study on human patients (postmenopausal women)	Dietary genistein (54 mg/day) may be as effective as hormone replacement therapy in attenuating menopause-related bone loss without causing the associated side effects.	[79]
	Epidemiologic study (63 257 Chinese men and women)	Consumption of soy food reduced the fracture risk in women to one-third.	[80]
	Blinded, randomized, crossover intervention trial in 24 postmenopausal women	A 50-day study showed daily intake of isoflavones (105 mg/day) increased bone calcium retention by 7.6% compared with that of risedronate at 15%, a bisphosphonate drug used for osteoporosis treatment.	[81]
Green tea (EGCG)	Ovariectomized 14-month-old female rats	Green tea supplementation resulted in increased femur bone mineral density via an increase in antioxidant capacity and a decrease of oxidative stress damage.	[82]
	Human bone marrow mesenchymal stem cells	EGCG can increase mRNA expression of BMP2 and subsequent osteogenic-related genes, including Runx2, ALP, osteonectin, and osteocalcin. EGCG further increased ALP activity and mineralization.	[83]