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Table 3: Studies regarding zinc supplementation and bone metabolism.
First author, year	Study design	Setting	Inclusion criteria	Eclusion criteria	Intervention	Parallel treatments	Number of subjects (M-F) If only	Duration of the intervention	Primary outcomes	Secondary outcomes	Results
Sadighi A, 2008	Randomized, double blind, placebo controlled clinical trial	Shohada Hospital of Tabriz, Iran	Men and women, aged 20-50 years old with traumatic long bone fracture	No history of osteoporosis, osteoarthritis, kidney stones, diabetes, and other endocrine disorders.taking any medication or supplementation known to influence bone metabolism or zinc status	One capsule of 220 mg zinc sulfate contain 50 mg zinc	Control group receiving placebo contain starch	60 (39 M, 21 F)	60 days	Determine the effect of zinc supplementation on fracture healing	Determine the relation between callus formation with zinc and alkaline phosphatase activity in serum	Significant change in callus formation if the group will compare to the control group after 60 days (Figure 3), and fracture healing was faster in the supplement group than control group
Nielsen FH, 2011	Double- blind, placebo- controlled design		Postmenopausal women aged 51-80 years, BMI ≤ 32 kg/m2, bone mineral density not more than 2·5 standard deviations below that for young adults; no collapsed/compressed vertebrae determined by using dual-energy X-ray absorptiometry (DXA); history of no menses for at least five years; and a circulating folliclestimulating hormone concentration, 40 IU/l Eligible applicants were invited to an information meeting	Use hormone replacement therapy for one year before the study, use medications that interfere with Ca absorption, have thyroid, liver and kidney disease	600 mg Ca supplement plus a 2 mg Cu (copper gluconate) and 12mg Zn (zinc gluconate) supplement	Supplement containing 600 mg Ca plus a maize starch placebo	649 M	2 years	Determine whether increased Zn intakes would reduce the risk for bone loss		The findings indicate that Zn supplementation may be beneficial to bone health in postmenopausal women with usual Zn intakes < 8,0 mg/d but not in women consuming adequate amounts of Zn
Strause L, 1994	Double- blind, placebo- controlled trial	San Diego greater Metropolitanarea	> 50 y old and in good general health	A positive Pap smear or mammogram during the previous year, any disease or condition known to affect bone or calcium metabolism, a history of chronic renal, hepatic or gastrointestinal disease, evidence of collapsed or focal vertebral sclerosis	Groups 2) placebo calcium, active trace minerals,- groups 3) active calcium, placebo trace minerals; and groups 4) active calcium, active trace minerals Subjects received placebo or 1,000 mg elemental calcium/d in the form of calcium citrate malate Each active supplement contained 15.0 mg of zinc as sulfate salt, 2.5 mg of copper, and 5.0 mg of manganese as gluconate salts	Groups: 1) placebo calcium, placebo trace minerals	59 F	2 years	Evaluate the impact of supplementary calcium with and without the addition of a combination of copper, manganese and zinc on spinal bone loss in healthy older post menopausal women		Older postmenopausal women supplemented with 1000 mg of calcium, 15 mg of zinc, 5 mg of manganese, and 2.5 mg of copper maintained spinal bone density and differed significantly from a placebo group that lost bone density Bone losses in the groups supplemented with trace mineral alone and with calcium alone were intermediate, but not significantly different from loss for either the placebo group or the group receiving calcium plus trace minerals
Nielsen FH, 2004	Randomized controlled trial	The metabolic unit of the Grand Forks Human Nutrition Research Center, Grand Forks, ND, USA	No underlying disease				25 post- menopausal women	200 days	To determine whether moderately high or low intakes of zinc adversely affect the copper status of postmenopausal women to result in unfavorable changes in calcium and magnesium metabolism and other indicators of bone turnover		Low dietary zinc (45.9 mmol/day; 3 mg/day) apparently resulted in undesirable changes in circulating calcitonin and osteocalcin The moderately high intake compared to the low intake of zinc increased the excretion of magnesium in the feces and urine, which resulted in a decreased magnesium balance
Ronaghy 1974	Clinical trial	Southern Iran	13-year-old prepubertal schoolboys		Grupo C) Zinc carbonate 40 mg + supplement of egg-white protein (10 g daily), corn oil, minerals, and vitamins	Grupo A) placebo Grupo B) supplement of egg-white protein (10 g daily), corn oil, minerals, and vitamins	49 boys 13-year-old prepubertal village schoolboys	18 months	To learn whether these failures could have been in part the result of administration of insufficient quantities of zinc as a dietary supplement		Significantly increased heights, weights, and bone ages occurred in those receiving the supplementary zinc During the 2nd year, bone development of the zinc-supplemented group surpassed that of the other groups by a substantial and statistically significant margin