Table 3.

Studies that considered copper supplementation.

First Author, Year	Study Design	Institution and Country	Inclusion Criteria	Intervention	Parallel Treatments	Number of Subjects (M-F) Mean Age	Duration of the Intervention	Primary Outcomes	Results
Nielsen FH, 2011 [30]	double-blind, placebo-controlled design.	University of North Dakota	postmenopausal women aged 51–80 y, BMI ≤ 32 kg/m2, BMD not more than 2·5 standard deviations below that for young adults	600 mg calcium (Ca) supplement plus a 2 mg Cu (copper gluconate) and 12 mg Zn (zinc gluconate) supplement.	supplement containing 600 mg Ca plus a maize starch placebo	649 F	2 years	How Cu and Zn intakes would reduce the risk for bone loss.	Cu supplementation apparently did not have an impact on whole-body bone contents, BMD.
Strause L, 1994 [31]	double-blind, placebo-controlled trial.	San Diego greater Metropolitan area	>50 y old and in good general health	(1) placebo Ca + active trace minerals, (2) active Ca + placebo trace minerals, (3) active Ca + active trace mineral: 1000 mg elemental calcium/d in the form of Ca citrate malate and active supplement contained 15.0 mg of Zn as sulfate salt, 2.5 mg of Cu, and 5.0 mg of manganese as gluconate salts.	placebo calcium + placebo trace minerals	59 F 66 ± 7 y	2 years	Impact of supplementary Ca with and without the addition of a combination trace elements on spinal bone loss.	Supplementation with 1000 mg of Ca, 15 mg of Zn, 5 mg of manganese, and 2.5 mg of Cu maintained spinal bone density and differed significantly from a placebo group that lost bone density.
Eaton-Evans 2003 [32]	random and double-blind study	Royal Victoria Hospital, north Belfast	healthy women, aged 45–56 years	3 mg Cu as amino acid chelate	placebo	73 F Cu group: 49.97± 3.1 Placebo group: 50.8 ± 3.5	2 years	Effects of Cu supplementation over 2 years on vertebral trabecular bone mineral density (VTBMD).	Cu supplementation appeared to have reduced the loss of VTBMD in these middle-aged women over a 2-year period.
Baker A 1999 [33]	longitudinal intervention trial	Institute of Food Research, Norwich, UK	Subjects without any history of bone or articular disease, and with no intake of medicine that could affect bone or cartilage metabolism	Medium (1.6 mg/d), low (0.7 mg/d) and high (6.0 mg/d) intakes of Cu, in that order. A 7 d rotating low Cu menu was formulated and analysed for Cu content. This low Cu diet (0.7 mg/d) was fed throughout the three dietary periods and was supplemented to the appropriate level of Cu (as a CuSO4 solution dissolved in de-mineralised water taken with a meal) to achieve the medium (1.6 mg/d) and high (6.0 mg/d) Cu intakes.	//////////	11 M 30.9 y	8-week dietary periods with a minimum of 4-week washout periods.	Effects of changing from a medium (1.6 mg Cu/d) to a low (0.7 mg Cu/d) or a high (6.0 mg/d) Cu intake on biochemical indices of bone turnover in healthy adult males.	Biomarkers of bone resorption were significantly increased when subjects were switched from the medium to the low Cu diet.