. 2017 Dec 26;318(24):2466–2482. doi: 10.1001/jama.2017.19344

Table 3. Subgroup Analysis of Association Between Vitamin D Supplementation and Fracture Incidence for Each Variable.

Variable	No. of Trials	No. of Participants		Fracture, RR (95% CI)	P Value^a
Variable	No. of Trials	With Fracture	Total	Fracture, RR (95% CI)	P Value^a
Hip Fracture (Primary Outcome)
Vitamin D dose and frequency
≥800 IU/d	3	91	2949	1.14 (0.76-1.72)	.48
<800 IU/d	1	106	2578	1.20 (0.83-1.75)
Intermittent high-dose (given as once every year)	3	145	11773	1.41 (1.02-1.96)
Intermittent high-dose (given as other frequencies^b)	2	46	3372	0.84 (0.48-1.50)
Sex
Women-only trials	4	38	3223	1.20 (0.64-2.26)	.99
Trials with men and women	5	350	17449	1.21 (0.98-1.49)	.99
Previous fractures
Yes	3	90	2820	1.09 (0.73-1.64)	.60
Other^c	5	296	17648	1.24 (0.99-1.55)	.60
Calcium intake, mg/d
≥900	2	36	2462	1.35 (0.70-2.59)	.80
<900	4	262	15390	1.23 (0.96-1.58)	.80
Baseline 25OHD, ng/mL
≥20	3	113	10330	1.49 (1.03-2.17)	.30
<20	4	229	7586	1.18 (0.91-1.52)	.30
Nonvertebral Fracture
Vitamin D dose and frequency
≥800 IU/d	3	369	2792	1.03 (0.85-1.24)	.72
<800 IU/d	0	0	0	Not estimable
Intermittent high-dose (given as once every year)	2	810	11698	1.13 (0.99-1.29)
Intermittent high-dose (given as other frequencies^b)	3	317	5953	1.12 (0.90-1.39)
Sex
Women-only trials	2	245	2944	1.20 (0.94-1.52)	.44
Trials with men and women	6	1251	17499	1.08 (0.97-1.20)	.44
Previous fractures
Yes	2	368	2745	1.02 (0.85-1.24)	.39
Other^c	6	1128	17698	1.13 (1.01-1.26)	.39
Calcium intake, mg/d
≥900	3	231	2464	1.22 (0.95-1.55)	.50
<900	3	897	15234	1.11 (0.97-1.26)	.50
Baseline 25OHD, ng/mL
≥20	4	898	15281	1.11 (0.98-1.26)	.88
<20	3	592	5092	1.09 (0.94-1.27)	.88
Vertebral Fracture
Vitamin D dose and frequency
≥800 IU/d	2	6	2745	1.51 (0.14-16.14)	.22
<800 IU/d	0	0	0	Not estimable
Intermittent high-dose (given as once every year)	1	63	2258	1.25 (0.76-2.03)
Intermittent high-dose (given as other frequencies^b)	1	46	2686	0.64 (0.36-1.15)
Sex
Women-only trials	1	63	2258	1.25 (0.76-2.03)	.52
Trials with men and women	3	52	5431	0.85 (0.29-2.47)	.52
Previous fractures
Yes	2	6	2745	1.51 (0.14-16.14)	.69
Other^c	2	109	4944	0.91 (0.48-1.75)	.69
Calcium intake, mg/d
≥900	1	63	2258	1.25 (0.76-2.03)	.09
<900	1	46	2686	0.64 (0.36-1.15)	.09
Baseline 25OHD, ng/mL
≥20	0	0	0	Not estimable	NA
<20	2	68	4933	1.34 (0.78-2.30)	NA
Total Fractures
Vitamin D dose and frequency
≥800 IU/d	7	404	4609	1.04 (0.86-1.25)	.15
<800 IU/d	1	257	2578	1.10 (0.87-1.39)
Intermittent high-dose (given as once every year)	2	285	2333	0.49 (0.04-5.88)
Intermittent high-dose (given as other frequencies^b)	4	298	3586	0.79 (0.64-0.99)
Sex
Women-only trials	4	317	3223	1.10 (0.75-1.62)	.55
Trials with men and women	10	927	9883	0.97 (0.84-1.12)	.55
Previous fractures
Yes	3	379	2820	0.81 (0.36-1.81)	.58
Other^c	9	848	10027	1.02 (0.85-1.23)	.58
Calcium intake, mg/d
≥900	4	298	2668	1.22 (0.98-1.51)	.16
<900	5	557	6310	0.94 (0.69-1.27)	.16
Baseline 25OHD, ng/mL
≥20	4	40	1242	1.12 (0.59-2.11)	.94
<20	6	919	7800	1.09 (0.91-1.31)	.94

Abbreviations: RR, relative risk; 25OHD, 25-hydroxyvitamin D.

^{^a}

P value for heterogeneity between subgroups.

^{^b}

Other frequencies include once every 3 or 4 months-and once every 1 week or month.

^{^c}

Includes previous no fracture, partial fracture, and missing fracture data.