Reference Study Country Duration Funding	Design	Subject characteristics at baseline (a)	Intervention (a)	Endpoint assessed Assay of serum 25(OH)D	Results	RoB Tier
Appel et al. (2021) STURDY USA Latitude 39° N 2 y (median 22.0 mo, range 0.4–31.3 mo) Mixed funding	RCT (Bayesian response‐adaptive in dose‐finding stage; parallel in best‐dose stage) Inclusion criteria: Community‐dwelling adults; aged ≥70 years; elevated fall risk (defined by self‐report of 1 or more of the following: 2 or more falls or at least 1 injurious fall in the past year, fear of falling due to balance or walking problems, difficulty maintaining balance, and use of an assistive device when walking); low serum 25(OH)D levels (not defined). Exclusion criteria: Cognitive impairment; hypercalcaemia; kidney, bladder, or ureteral stones; use of supplemental vitamin D in doses higher than 1000 IU/d [25 μg/d] or calcium in doses higher than 1200 mg/d. Persons using 1000 IU/d [25 μg/d] or less of supplemental vitamin D had to agree to maintain this dosage. N participants, randomised/completed/analysed Dose‐finding stage (Oct 2015 to Mar 2018): G1: 256/NR/NR G2: 121/118/121 G3: 68/66/68 G4: 69/66/69 Best‐dose stage1) (Apr 2018 to May 2019): G1: +38 = 339/329/339 G2–G4: +91 = 349/338/ITT 349, PP 308 1) New recruited participants + participants participating in the dose‐finding stage; recruitment was ongoing throughout Oct 2015 to Feb 2019; not all analysed participants underwent at least 12 mo intervention, as interpreted from Supplementary Tables 2 and 3.	Sex (% females) G1: 43.0 G2: 47.1 G3: 42.6 G4: 40.6 Age (y) G1: 77.5 ± 5.6 G2: 76.4 ± 4.8 G3: 77.3 ± 4.6 G4: 79.1 ± 5.9 Serum 25(OH)D (nmol/L) G1: 54.8 ± 31.2 G2: 56.3 ± 10.7 G3: 52.5 ± 13.1 G4: 53.6 ± 12.4 BMI (kg/m2) G1: 30.3 ± 6.4 G2: 30.5 ± 5.3 G3: 30.7 ± 6.4 G4: 30.3 ± 6.2 Ethnicity (%) White: G1: 83.6 G2: 71.7 G3: 76.1 G4: 82.6 Black: G1: 15.6 G2: 25.0 G3: 22.4 G4: 14.5 Other: G1: 2.0 G2: 7.5 G3: 3.0 G4: 2.9 Smoking status: NR Alcohol use: NR Health status – Frailty (%) Robust: G1: 31.2 G2: 25.8 G3: 36.8 G4: 26.1 Pre‐frail: G1: 57.8 G2: 60.8 G3: 52.9 G4: 58.0 Frail: G1: 10.9 G2: 13.3 G3: 10.3 G4: 15.9 Fallen at least once in prior year (%) G1: 63.3 G2: 62.0 G3: 63.2 G4: 68.1 Season: Oct 2015 to May 2019.	Vitamin D3 Doses Dose‐finding stage: G1: vitamin D3 200 IU/d [5 μg/d] G2: vitamin D3 1000 IU/d [25 μg/d] G3: vitamin D3 2000 IU/d [50 μg/d] G4: vitamin D3 4000 IU/d [100 μg/d] Best‐dose stage:1,2) G1: vitamin D3 200 IU/d [5 μg/d] G2–G4: vitamin D3 1000 IU/d [25 μg/d] 2) Newly recruited participants and the participants in G3 and G4 were assigned vitamin D3 1000 IU/d [25 μg/d]. Background vitamin D intake (IU/d) G1: 307 (647) IU/d [7.68 (16.2) μg/d] G2: 293 (702) IU/d [7.33 (17.6) μg/d] G3: 345 (779) IU/d [8.63 (19.5) μg/d] G4: 237 (520) IU/d [5.93 (13.0) μg/d] Background vitamin D supplement use (%) G1: 37.5 G2: 39.7 G3: 39.7 G4: 33.3 Background calcium intake: NR Compliance Pill count method (%) At least 80% of daily pills taken: G1: 75.8 G2–G4: 72.5 50%–79% of daily pills taken: G1: 13.9 G2–G4: 11.5 25%–49% of daily pills taken: G1: 4.4 G2–G4: 8.0 Less than 25% of daily pills taken: G1: 5.9 G2–G4: 8.0 Serum 25(OH)D (nmol/L) During dose‐finding at 12 mo: G1: 68.3 ± 17.9 G2: 81.0 ± 16.7 G3: 83.3 ± 17.9 G4: 123.2 ± 36.9 During dose‐finding + best dose stages at 24 mo: G1: 70.4 ± 16.6 G2–G4: 99.2 ± 29.9	Falls ‐ defined as any fall, slip, or trip in which the participant lost his or her balance and landed on the floor or ground or at a lower level. ‐ surveillance methods: monthly calendars, scheduled clinic visits and telephone calls, and ad hoc telephone contacts (participants were instructed to call the clinic if they fell); participants were asked to document on their study calendar each day whether a fall occurred and to mail their calendar each month ‐ when a fall was reported, staff called the participant to obtain additional information. Serious falls ‐ defined as a fall resulting in a dislocated, broken, or fractured body part, or a fall associated with a serious adverse event. **** Assay of serum 25(OH)D: HPLC–MS/MS	Data extracted: ITT Dose‐finding stage ‐ Falls First fall during dose‐finding, n of participants G1: 123 G2: 43 G3: 41 G4: 41 First fall during dose‐finding, rate per 100 person‐years (95% CI) G1: 88.3 (74.0, 105.4) G2: 70.5 (52.3, 95.0) G3: 103.0 (75.8, 139.9) G4: 99.4 (73.2, 135.0) First fall during dose‐finding, HR (95% CI) G2 vs G1: 0.80 (0.57, 1.14) G3 vs G1: 1.20 (0.84, 1.71) G4 vs G1: 1.16 (0.82, 1.65) G3 vs G2: 1.50 (0.98, 2.31) G4 vs G2: 1.45 (0.94, 2.22) Dose‐finding stage – Serious falls First serious fall during dose‐finding, n of participants G1: 12 G2: 4 G3: 5 G4: 6 First fall with hospitalization during dose‐finding, n of participants G1: 6 G2: 2 G3: 5 G4: 1 First serious fall during dose‐finding, rate per 100 person‐years (95% CI) G1: 5.4 (3.1, 9.5) G2: 4.9 (1.8, 13.1) G3: 7.3 (3.0, 17.5) G4: 8.9 (4.0, 19.9) First fall with hospitalization during dose‐finding, rate per 100 person‐years (95% CI) G1: 2.7 (1.2, 5.9) G2: 2.4 (0.6, 9.6) G3: 7.3 (3.0, 17.5) G4: 1.4 (0.2, 10.1) First serious fall during dose‐finding, HR (95% CI) G2 vs G1: 0.91 (0.29, 2.81) G3 vs G1: 1.37 (0.48, 3.89) G4 vs G1: 1.68 (0.63, 4.48) First fall with hospitalization during dose‐finding, HR (95% CI) G2 vs G1: 0.86 (0.17, 4.29) G3 vs G1: 2.84 (0.87, 9.30) G4 vs G1: 0.55 (0.07, 4.60) Dose‐finding + best‐dose stages ‐ Falls First fall over 2 y, n of participants G1: 208 G2–G4: 215 First fall over 2 y, rate per 100 person‐years (95% CI) G1: 74.8 (65.3, 85.7) G2–G4: 77.4 (67.8, 88.5) First fall over 2 y, HR (95% CI) G2–G4 vs G1: 1.05 (0.87, 1.27) Data extracted: PP Dose‐finding + best‐dose stages‐ Falls First fall over 2 y, n of participants G1: 208 G2–G4: 157 First fall over 2 y, rate per 100 person‐years (95% CI) G1: 74.8 (65.3, 85.7) G2–G4: 77.6 (66.3, 90.7) First fall over 2 y, HR (95% CI) G2–G4 vs G1: 0.96 (0.78, 1.18)	2
Bischoff‐Ferrari et al. (2020); Bischoff‐Ferrari et al. (2022) DO‐HEALTH Switzerland, Germany, Austria, France, and Portugal Latitude NA 3 y Mixed funding	RCT (parallel) Inclusion criteria: Generally healthy, ≥70 years old and community dwelling; no major health events (i.e. cancer or myocardial infarction) in the 5 y prior to enrolment; sufficient mobility to come to the study centres without help; a Mini‐Mental State Examination score of ≥24; able to swallow study capsules; able and willing to participate, sign informed consent (including consent to analyze all samples until drop‐out or withdrawal) and cooperate with study procedures. Recruitment was conducted with the goal of including ≥40% of participants with a history of falling in the prior 12 mo to increase representation of older adults at higher risk of frailty. Exclusion criteria: Taking >1000 IU/d [25 μg/d] of vitamin D in supplements during the 36 mo prior to enrolment or being unwilling to limit vitamin D supplement intake to 800 IU/d [20 μg/d] and calcium supplementation to 500 mg/d during trial; taking omega‐3 supplements during the 3 mo prior to enrolment and/or being unwilling to avoid them during the trial; use of any active vitamin D metabolite, PTH treatment, or calcitonin at baseline and unwillingness to forego these treatments during the course of the trial; current or recent (previous 4 mo) participation in another clinical trial, or plans of such participation in the next 3 years (corresponding to DO‐HEALTH length); presence of the following diagnosed health conditions in the last 5 years: history of cancer (except non‐melanoma skin cancer), myocardial infarction, stroke, transient ischemic attack, angina pectoris, or coronary artery intervention; severe renal impairment (creatinine clearance ≤15 ml/min) or dialysis, hypercalcaemia (>2.6 mmol/l); hemiplegia or other severe gait impairment; history of hypo‐ or primary hyperparathyroidism; severe liver disease; history of granulomatous diseases (i.e. tuberculosis, sarcoidosis); major visual or hearing impairment or other serious illness that would preclude participation; living with a partner who is enrolled in DO‐HEALTH (i.e. only one person per household can be enrolled); living in assisted living situations or a nursing home; epilepsy and/or use of anti‐epileptic drugs; individuals who fell more than 3 times in the last month; osteodystrophia deformans (M. Paget, Paget's disease); for study center in Germany only: persons who were institutionalized / in prison by court order. Temporary exclusion: acute fracture in the last 6 weeks. N participants randomised/completed/analysed G1–G4: 1081/907/1081 G5–G8: 1076/938/1076	Sex (% females) G1–G4: 61.4 G5–G8: 62.0 Age (y) G1–G4: 74.9 ± 4.4 G5–G8: 75.0 ± 4.5 Serum 25(OH)D (ng/mL) G1–G4: 22.4 ± 8.5 ng/mL [56 ± 21.25 nmol/L] G5–G8: 22.4 ± 8.4 ng/mL [56 ± 21 nmol/L] BMI (kg/m2) G1–G4: 26.2 ± 4.2 G5–G8: 26.5 ± 4.4 Ethnicity [assumed]: Majority Caucasian Smoking status: NR Alcohol use: NR Health status: Generally healthy Fallen in prior year (%) G1: 42.3 G2: 41.4 Season: NR	Vitamin D3 Doses G1: double placebo + CEP G2: double placebo + SHEP G3: vitamin D placebo + omega‐3 fatty acids 1 g/d + CEP G4: vitamin D placebo + omega‐3 fatty acids 1 g/d + SHEP G5: vitamin D3 2000 IU/d [50 μg/d] + omega‐3 fatty acid placebo + CEP G6: vitamin D3 2000 IU/d [50 μg/d] + omega‐3 fatty acid placebo + SHEP G7: vitamin D3 2000 IU/d [50 μg/d] + omega‐3 fatty acids 1 g/d + CEP G8: vitamin D3 2000 IU/d [50 μg/d] + omega‐3 fatty acids 1 g/d + SHEP CEP = control exercise program; SHEP = simple home strength exercise program. Background vitamin D intake: NR Background vitamin D supplement use, ≥800 IU [20 μg] (%) G1–G4: 11.7 G5–G8: 10.2 Background calcium intake: NR Compliance Pill count method – at least 80% of total study pills taken (%) All: 85.8 Serum 25(OH)D at 3 y (ng/mL) G1–G4: 24.4 ng/mL [61 nmol/L] on average G5–G8: 37.6 ng/mL [94 nmol/L] on average.	Fractures ‐ nonvertebral ‐ confirmed by x‐ray reports or medical records describing an x‐ray report or repair of the fracture. Falls ‐ defined as unintentionally coming to rest on the ground, floor, or other lower level ‐ recorded at each 3‐mo in‐person contact by asking participants whether they had sustained a fall in the last 3 mo; was supported by a fall diary ‐ fall protocol collected information on the fall circumstances, related injuries, treatment, and related health‐care utilization. Injurious falls ‐ defined as falls leading to any injury. **** Assay of serum 25(OH)D: LC–MS	Data extracted: unclear Fractures Fractures over 3 years, n of events G1–G4: 127 G5–G8: 129 Fractures, unadjusted IRR (99% CI) G5–G8 vs G1–G4: 1.02 (0.74, 1.40) Fractures, adjusted IRR (99% CI) 3) G5–G8 vs G1–G4: 1.03 (0.75, 1.43) Data extracted: ITT Falls Falls over 3 years, n of events G1–G4: 1673 G5–G8: 1660 ≥1 fall over 3 years, n of participants G1–G4: 654 G5–G8: 657 Falls, unadjusted IRR (95% CI) G5–G8 vs G1–G4: 1.00 (0.90, 1.12) Falls, adjusted IRR (95% CI) 4) G5–G8 vs G1–G4: 1.03 (0.92, 1.14) ≥ 1 fall, unadjusted OR (95% CI) G5–G8 vs G1–G4: 1.02 (0.85, 1.22) ≥ 1 fall, adjusted OR (95% CI) 4) G5–G8 vs G1–G4: 1.02 (0.85, 1.23). Injurious falls Injurious falls over 3 y, n of events G1–G4: 1068 G5–G8: 1073 ≥1 injurious fall over 3 y, n of participants G1–G4: 548 G5–G8: 570 Injurious falls, unadjusted IRR (95% CI) G5–G8 vs G1–G4: 1.01 (0.90, 1.13) Injurious falls, adjusted IRR (95% CI) 4) G5–G8 vs G1–G4: 1.03 (0.92, 1.14). ≥ 1 injurious fall, unadjusted OR (95% CI) G5–G8 vs G1–G4: 1.10 (0.92, 1.30) ≥ 1 injurious fall, adjusted OR (95% CI) 4) G5–G8 vs G1–G4: 1.11 (0.93, 1.33). 3) adjusted for age, sex, prior falls, BMI, and study site. 4) adjusted for study site, sex, age, previous fall, baseline BMI, and baseline use of walking aids.	1 for fractures; 2 for falls
Burt et al. (2019) Canada Latitude [assumed] 51.05° N 3 y Private funding	RCT (parallel) Inclusion criteria: Healthy men and women aged 55–70 years; DXA lumbar spine and total hip areal BMD T score greater than −2.5 SD, serum 25(OH)D between 30–125 nmol/L, and normal serum calcium (2.10–2.55 mmol/L). Participants were requested to take no more than 200 IU [5 μg] per day of additional vitamin D (eg. a multivitamin supplement). Exclusion criteria: Serum25(OH)D < 30 nmol/L or > 125 nmol/L; serum calcium >2.55 mmol/L or <2.10 mmol/L; vitamin D supplement use >2000 IU/d [50 μg/d] for the past 6 mo; use of bone active medication within the last 2 y; disorders known to affect vitamin D metabolism such as sarcoidosis, renal failure, malabsorption disorders, kidney stone within the past 2 y, or regular use of tanning salons; DXA T score compatible with osteoporosis at the lumbar spine, total hip or femoral neck; and high 10‐year risk (≥20%) for osteoporotic fracture (as defined by the World Health Organization's Canadian FRAX calculator). N participants, randomised/completed/analysed: G1: 109/100/105 G2: 100/94/97 G3: 102/93/101	Sex: (% females) G1: 42.9 G2: 48.5 G3: 47.5 Age (y) G1: 62.2 ± 4.2 G2: 62.6 ± 4.3 G3: 61.9 ± 4.1 Years since menopause G1: 12.6 ± 5.9 G2: 11.7 ± 7.3 G3: 12.5 ± 5.6 Serum 25(OH)D (nmol/L) G1: 76.7 ± 21.0 G2: 81.3 ± 20.1 G3: 78.4 ± 18.4 BMI (kg/m2) G1: 27.7 ± 4.3 G2: 28.1 ± 5.0 G3: 27.1 ± 4.1 Ethnicity (%) Non‐Hispanic White: G1: 93.3 G2: 96.9 G3: 97.0 Non‐Hispanic black: G1: 1.0 G2: 1.0 G3: 0 Asian: G1: 4.7 G2: 2.1 G3: 2.0 Hispanic: G1: 1.0 G2: 0 G3: 1.0 Smokers (%) G1: 1.9 G2: 0 G3: 4.0 Alcohol use: NR Health status: NR Fracture experienced after age 50 y (%) G1: 16.2 G2: 13.4 G3: 16.8 Falls in the last year (%) G1: 21.0 G2: 20.6 G3: 17.8 Season: Aug 2013 to Dec 2017.	Vitamin D3 Doses: G1: vitamin D3 400 IU/d [10 μg/d] G2: vitamin D3 4000 IU/d [100 μg/d] G3: vitamin D3 10 000 IU/d [250 μg/d] Participants not consuming the recommended dietary allowance of calcium (1200 mg/d) received calcium tablets as needed (≤maximum of 600 mg/d) to approximate a total daily intake of 1200 mg. Background vitamin D intake: NR Background calcium intake: NR Compliance Pill count method – number of days of supplement administration vs total number of days (%) All: 99 on average, range (range 81–100). Serum 25(OH)D at 36 mo (nmol/L) G1: 77.4 ± 17.9 G2: 132.2 ± 28.0 G3: 144.4 ± 40.4	Fractures ‐ reported as adverse events ‐ reviewed by study clinicians via participant medical records and x‐ray reports where available ‐ fractures of fingers or toes and traumatic fractures were not included. Low‐trauma (fragility) fractures: ‐reported as adverse events ‐ defined as resulting from low trauma, such as a fall from standing height or less. Falls ‐ reported as adverse events ‐ adjudicated by the study physicians. **** Assay of serum 25(OH)D: CLIA (DiaSorin Liaison XL system)	Data extracted: unclear Low‐trauma fractures Low‐trauma fractures over 3 y, n of events G1: 4 G2: 3 G3: 5 ≥ 1 low‐trauma fracture over 3 y, n of participants G1: 4 G2: 3 G3: 5 Falls Falls over 3 y, n of events G1: 4 G2: 11 G3: 6 ≥ 1 fall over 3 y, n of participants G1: 4 G2: 10 G3: 5 Stated that no significant difference in falls detected among the 3 groups.	1
Flicker et al. (2005) Australia Latitude 32° S, 34° S, 38° S [study residents in three states] 2 y Mixed funding	RCT (parallel) Inclusion criteria: Older people resident in hostels and nursing homes in urban and rural centers; 25(OH)D level > 25 nmol/L and < 90 nmol/L. Exclusion criteria: 25(OH)D level < 25 nmol/L or > 90 nmol/L; use of agents that could affect bone and mineral metabolism, such as warfarin, chronic heparin therapy, vitamin D therapy within the previous 3 mo, glucocorticoids at an average daily dose of >5 mg prednisolone (or equivalent) for >1 mo within the preceding year; current use of bisphosphonates, and hormone replacement therapy; thyrotoxicosis within the previous 3 years, primary hyperparathyroidism treated within the previous 3 years, multiple myeloma, Paget's disease of bone, a history of malabsorption, intercurrent active malignancy, and other disorders affecting bone and mineral metabolism. N participants randomised/completed/analysed G1: 312/unclear/ITT 312, PP 271 5) G2: 313/unclear/ITT 313, PP 269 5) 5) those whose vitamin D compliance was ≥50%	Sex (% females) G1: 95 G2: 95 Age (y) G1: 83.3 ± 8.8 G2: 83.6 ± 7.8 Serum 25(OH)D (%) 25–40 nmol/L: G1: 54 G2: 61 41–60 nmol/L: G1: 35 G2: 28 61–90 nmol/L: G1: 11 G2: 11 BMI: NR Ethnicity [assumed]: Majority Caucasian Smoking status: NR Alcohol use: NR Health status: NR Previous fracture (%) Hip: G1: 12 G2: 17 Colles: G1: 5 G2: 3 Recorded vertebral: G1: 6 G2: 4 Other: G1: 7 G2: 9 Any: G1: 24 G2: 27 Season: NR	Vitamin D2 Doses G1: placebo + calcium 600 mg/d G2: vitamin D2 10 000 IU/wk [250 μg/wk = 35.71 μg/d] until Nov 1998; thereafter 1000 IU/d [=25 μg/d] 6) + calcium 600 mg/d. 6) due to the discontinuation of the preparation of commercial 10 000 IU [250 μg] vitamin D2 tablets. Background vitamin D intake: NR Background calcium intake: NR Background calcium supplement use (%) G1: 5 G2: 4 Compliance Pill count method ‐ vitamin D supplements removed from the participant's medication container (%) 0–25%: G1: 5 G2: 4 26–50%: G1: 7 G2: 7 51–75%: G1: 21 G2: 18 76–100%: G1: 66 G2: 68 Unknown: G1: 1 G2: 3 Serum 25(OH)D at 2 yr: NR	Fractures ‐ verified using x‐ray report when possible. Falls ‐ defined as an event that results in a person coming to rest inadvertently on the ground or other lower level ‐ recorded by residential care staff prospectively in diaries. **** Assay of serum 25(OH)D: NR	Data extracted: ITT Fractures ≥ 1 fracture over 2 y, n of participants G1: 35 G2: 25 ≥ 1 fracture, OR (95% CI) G2 vs G1: 0.69 (0.40, 1.18) Falls Falls over 2 y, n of events G1: 890 G2: 665 ≥ 1 fall over 2 y, n of participants G1: 185 G2: 170 Falls, IRR (95% CI) G2 vs G1: 0.73 (0.57, 0.95) ≥ 1 fall, OR (95% CI) G2 vs G1: 0.82 (0.59, 1.12) Data extracted: PP 5) Fractures ≥ 1 fracture over 2 y, n of participants G1: 30 G2: 21 ≥ 1 fracture, OR (95% CI) G2 vs G1: 0.68 (0.38, 1.22) Falls Falls over 2 y, n of events G1: 862 G2: 570 ≥ 1 fall over 2 y, n of participants G1: 176 G2: 152 Falls, IRR (95% CI) G2 vs G1: 0.63 (0.48, 0.82) ≥ 1 fall, OR (95% CI) G2 vs G1: 0.70 (0.50, 0.99) 5) those whose vitamin D compliance was ≥50%	2
Grant et al. (2005) RECORD United Kingdom Latitude [assumed] 51° N to 58° N; the trial was based in 21 hospitals in United Kingdom 24 to 62 mo (median 45, IQR 37–52) Mixed funding	RCT (parallel) Inclusion criteria: People aged ≥70 years who had had a low trauma, osteoporotic fracture in the previous 10 years. Exclusion criteria: Bed or chair bound before fracture; cognitive impairment indicated by an abbreviated mental test score of <7; cancer in the past 10 years that was likely to metastasise to bone; fracture associated with pre‐existing local bone abnormality; those known to have hypercalcaemia; renal stone in the past 10 years; life expectancy of <6 mo; individuals known to be leaving the UK; daily intake of >200 IU [5 μg/d] vitamin D or > 500 mg calcium supplements; intake in the past 5 years of fluoride, bisphosphonates, calcitonin, tibolone, hormone replacement therapy, selective oestrogen‐receptor modulators, or any vitamin D metabolite (eg, calcitriol); and vitamin D by injection in the past year. N participants randomised/completed/analysed G1–G2: 2643/2382 at 24 mo, 572 at 48 mo, 29 at 60 mo /2382 at 24 mo, 572 at 48 mo, 29 at 60 mo G3–G4: 2649/2401 at 24 mo, 582 at 48 mo, 24 at 60 mo /2401 at 24 mo, 582 at 48 mo, 24 at 60 mo	Sex (% females) G1–G2: 85 G3–G4: 85 Age (y) G1–G2: 77 ± 6 G3–G4: 77 ± 6 Serum 25(OH)D (ng/mL) All: 15.2 ± 6.5 ng/mL [38 ± 16.25 nmol/L] NR across groups. BMI: NR Ethnicity (%) White: G1–G2: 99 G3–G4: 99 Smoking status (%) Current smokers: G1–G2: 12.1 G3–G4: 11.3 Alcohol use: NR Health status: A history of low‐trauma, osteoporotic fracture in the previous 10 years. An osteoporotic fracture was defined as a fracture due to a fall from no more than standing height, or as a definite clinical event with radiologist‐confirmed evidence of a vertebral fracture. Previous fracture since age 50 y (%) G1: 35.3 G2: 35.0 Season: Feb 1999 to March 2002.	Vitamin D3 Doses G1: double placebo G2: vitamin D placebo + calcium 1000 mg/d G3: vitamin D3 800 IU/d [20 μg/d] + calcium placebo G4: vitamin D3 800 IU/d [20 μg/d] + calcium 1000 mg/d Background vitamin D intake: NR Background calcium intake: NR Compliance Pill count method – taking tablets >80% of days at 24 mo (%): G1–G2: 78.8 G3–G4: 78.4 Completing questionnaires >80% of days at 24 mo (%): G1–G2: 59.9 G3–G4: 60.6 Serum 25(OH)D, change over 1 yr (ng/mL) G1: +3.1 ± 7.2 ng/mL [7.75 ± 18 nmol/L] G2: +1.4 ± 5.7 ng/mL [3.5 ± 14.25 nmol/L] G3: +9.7 ± 8.7 ng/mL [24.25 ± 21.75 nmol/L] G4: +9.6 ± 6.9 ng/mL [24.0 ± 17.25 nmol/L]	Fractures ‐ clinical, radiological confirmed vertebral fractures excluding those of the face or skull ‐ were obtained from postal questionnaires every 4 mo with telephone follow‐up if needed, hospital and general practice staff, nominated friends or relatives of participants, and national routine data‐collection systems of the UK Office of National Statistics, the Information and Statistics Division (Scotland), and the Hospital Episode Statistics gathered by the Department of Health in England ‐ confirmation always sought from a second source. Falls ‐ defined by means of the question” Have you fallen during the last week?” ‐ obtained from the postal questionnaires and were supplemented by further clinical information on potentially serious adverse events. **** Assay of serum 25(OH)D: HPLC	Data extracted: ITT New fractures New fractures over the intervention, n of participants G1–G2: 385 G3–G4: 396 New fractures, HR (95% CI) G3–G4 vs G1–G2: 1.01 (0.88, 1.17) Confirmed fractures Confirmed fractures over the intervention, n of participants G1–G2: 377 G3–G4: 387 Confirmed fractures, HR (95% CI) G3–G4 vs G1–G2: 1.01 (0.87, 1.16) Low‐trauma fractures Low‐trauma fractures over the intervention, n of participants G1–G2: 345 G3–G4: 353 Low‐trauma fractures, HR (95% CI) G3–G4 vs G1–G2: 1.02 (0.88, 1.19) Falls Falls over the intervention, n of participants G1–G2: 381 G3–G4: 380 Falls, HR (95% CI) G3–G4 vs G1–G2: 0.97 (0.84, 1.12)	2
Hin et al. (2016) BEST‐D United Kingdom Latitude [assumed] 51° N to 58° N 12 mo Mixed funding	RCT (parallel) Inclusion criteria: Ambulatory, aged 65 y or more, living in the community, not currently taking more than 10 μg/d vitamin D3. Exclusion criteria: Nursing home residents; regular users of vitamin D supplements more than 10 μg/d; prescribed calcium supplements, bisphosphonates, parathyroid hormone (PTH), or calcitonin; had medically diagnosed dementia or history of hypercalcaemia, hyperparathyroidism, lymphoma, sarcoidosis, active tuberculosis or renal calculus; judged by own doctor as likely to be poorly compliant with clinic visits or medication; or a history of alcohol or substance misuse or a history that might limit the ability to take the study treatment (e.g. terminal illness). N participants randomised/completed/analysed G1: 101/95/101 G2: 102/98/102 G3: 102/97/102	Sex (% females) G1: 49 G2: 50 G3: 49 Age (y) G1: 72 ± 6 G2: 72 ± 6 G3: 71 ± 6 Serum 25(OH)D (nmol/L) G1: 47 ± 1.5 G2: 55 ± 2.2 G3: 49 ± 1.5 BMI (kg/m2) G1: 28 ± 5 G2: 27 ± 4 G3: 27 ± 5 Ethnicity: White Smoking status (%) Current smokers: G1: 7 G2: 7 G3: 7 Alcohol use: NR Health status (%) Hypertension: G1: 35 G2: 43 G3: 39 Diabetes: G1: 9 G2: 9 G3: 9 Fracture experienced ever (%) G1: 30 G2: 29 G3: 30 Any fall in the past 6 mo (%) G1: 12 G2: 15 G3: 13 Season: Randomisation occurred between Sept 2012 and March 2013.	Vitamin D3 Doses G1: placebo G2: vitamin D3 2000 IU/d [50 μg/d] G3: vitamin D3 4000 IU/d [100 μg/d] Background vitamin D intake: NR Background vitamin D supplement use ≤10 μg/d (%) G1: 13 G2: 10 G3: 12 Background calcium intake (mg/d) G1: 713 ± 302 G2: 695 ± 292 G3: 724 ± 287 Background calcium supplement use (%) G1: 4 G2: 1 G3: 4 Compliance Pill count method – capsules taken on all or most days (%) At 6 mo: G1: 87 G2: 93 G3: 93 At 12 mo: G1: 85 G2: 92 G3: 90 Serum 25(OH)D at 12 mo (nmol/L) G1: 53 ± 2.4 G2: 102 ± 2.4 G3: 137 ± 2.4	Fractures ‐ self‐reported ‐ measured at all sites and specific sites ‐ recorded at 6 and 12 mo ‐ no additional information provided. Falls ‐ self‐reported ‐ recorded at 6 and 12 mo ‐ no additional information provided. **** Assay of serum 25(OH)D: CLIA (Beckman Coulter Ltd., High Wycombe, England).	Data extracted: ITT Any fracture, n of participants G1: 1 G2–G3: 6 P = 0.31 for difference in numbers between groups. Any fall, n of participants G1: 14 G2–G3: 34 P = 0.53 for difference in numbers between groups.	2
LeBoff et al. (2020a) VITAL USA Latitude [assumed] 19° N to 64.9° N; this was a nationwide study 5 y, (median 5.3, range 3.8–6.1) Mixed funding	RCT (parallel) Inclusion criteria: Men age ≥ 50 and women age ≥ 55 years. Exclusion criteria: A history of cancer or cardiovascular disease; cirrhosis, hypercalcaemia, renal failure or dialysis, and other serious conditions. Personal use of vitamin D3 was limited to 800 IU/d [20 μg/d] or less and 1200 mg/day or less for calcium. N participants randomised/completed/analysed G1–G2: 12944/NR/12867 at baseline, 12119 at year 1, 11861 at year 2, 11334 at year 3, 10764 at year 4, 9960 at year 5 G3–G4: 12927/NR/12848 at baseline, 12168 at year 1, 11879 at year 2, 11410 at year 3, 10914 at year 4, 10099 at year 5	Sex (% females) G1–G2: 50.5 G3–G4: 50.7 Age (y) G1–G2: 67.14 ± 7.08 G3–G4: 67.13 ± 7.05 Serum 25(OH)D (nmol/L) G1–G2: 76.6 ± 25 G3–G4: 76.8 ± 25 BMI (kg/m2) G1–G2: 28.07 ± 5.79 G3–G4: 28.12 ± 5.68 Ethnicity (%) Non‐hispanic white: G1–G2: 71.4 G3–G4: 71.3 Black: G1–G2: 20.2 G3–G4: 20.2 Non‐black Hispanic: G1–G2: 3.9 G3–G4: 4.08 Asian: G1–G2: 1.6 G3–G4: 1.5 Native American or Alaskan native: G1–G2: 0.87 G3–G4: 0.92 Other or unknown: G1–G2: 2.09 G3–G4: 2.05 Smoking status (%) Current smokers: G1–G2: 7.2 G3–G4: 7.2 Alcohol use (%) Never: G1–G2: 31.6 G3–G4: 31.3 Rarely to weekly: G1–G2: 7.6 G3–G4: 7.4 1‐6/wk: G1–G2: 34.4 G3–G4: 35.5 Daily: G1–G2: 26.4 G3–G4: 25.8 Health status (%) ”In general would you say your health is…” Excellent: G1–G2: 28.9 G3–G4: 29.3 Very good: G1–G2: 45.0 G3–G4: 44.5 Good: G1–G2: 22.5 G3–G4: 22.3 Fair: G1–G2: 3.4 G3–G4: 3.8 Poor: G1–G2: 0.27 G3–G4: 0.22 History of fragility fracture (%) G1: 9.97 G2: 9.96 Fallen in prior year (%) G1: 32.6 G2: 33.8 Season: NR	Vitamin D3 Doses G1: double placebo G2: vitamin D placebo + omega‐3 fatty acids 1 g/d G3: vitamin D3 2000 IU/d [50 μg/d] + omega‐3 fatty acid placebo G4: vitamin D3 2000 IU/d [50 μg/d] + omega‐3 fatty acids 1 g/d Background dietary vitamin D intake: NR Background vitamin D intake ≤800 IU/d [20 μg/d] (%): G1–G2: 42.8 G3–G4: 42.5 Background dietary calcium intake: NR Background calcium intake ≤1200 mg/d (%): G1–G2: 19.6 G3–G4: 20.3 Compliance Pill count method – those taking ≥2/3 of the trial capsules (%) Among those answering a compliance question by questionnaire: G1–G2: 84.7 G3–G4: 85.9 Among all participants including nonrespondents to questionnaires: G1–G2: 74. G3–G4: 76.1 Serum 25(OH)D at 1 yr (nmol/L) G1–G2: NR G3–G4: 104 on average	Falls ‐ defined as unintentionally coming to rest on the ground, floor, or lower surface ‐ numbers were recorded in questionnaires by the participants. Injurious falls ‐ defined as those resulting in limited regular activity for ≥1 day or in a doctor visit. Falls requiring hospitalization or being evaluated by a health care provider ‐ yes/no ≥ 2 falls was selected as the main outcome. Single falls without injury was not included. **** Assay of serum 25(OH)D: LC–MS/MS	Data extracted: ITT Falls ≥ 2 falls, n/N Year 1 G1–G2: 1059/12119 G3–G4: 1075/12168 Year 2 G1–G2: 1158/11861 G3–G4: 1167/11879 Year 3 G1–G2: 1130/11334 G3–G4: 1155/11410 Year 4 G1–G2: 1048/10764 G3–G4: 1102/10914 Year 5 G1–G2: 1127/9960 G3–G4: 1202/10099 ≥ 2 falls, OR (95% CI), average proportions per year over 5 years G3–G4 vs G1–G2: 0.97 (0.90, 1.05) Injurious falls ≥ 1 injurious fall, n/N Year 1 G1–G2: 823/12119 G3–G4: 811/12168 Year 2 G1–G2: 855/11861 G3–G4: 831/11879 Year 3 G1–G2: 814/11334 G3–G4: 877/11410 Year 4 G1–G2: 788/10764 G3–G4: 818/10914 Year 5 G1–G2: 945/9960 G3–G4: 1005/10099 ≥ 1 fall resulting in injury, OR (95% CI), average proportions per year over 5 years G3–G4 vs G1–G2: 1.03 (0.94, 1.13) Falls requiring hospitalization ≥ 1 fall requiring hospitalization, n/N Year 1 G1–G2: 588/12119 G3–G4: 544/12168 Year 2 G1–G2: 588/11861 G3–G4: 566/11879 Year 3 G1–G2: 550/11334 G3–G4: 595/11410 Year 4 G1–G2: 554/10764 G3–G4: 570/10914 Year 5 G1–G2: 666/9960 G3–G4: 732/10099 ≥ 1 fall resulting in hospital, OR (95% CI), average proportions per year over 5 years G3–G4 vs G1–G2: 1.04 (0.90, 1.19)	2
Macdonald et al. (2013) United Kingdom Latitude 57° N 1 yr Mixed funding	RCT (parallel) Inclusion criteria: Healthy postmenopausal, non‐smoking women aged 60–70 years; not suffering from any condition (diabetes, asthma, malabsorption, blood pressure > 160 mmHg systolic or > 99 mmHg diastolic); not taking medication (hypotensive, hypolipemic, ant‐inflammatory, oral corticosteroid) likely to affect vitamin D metabolism or cardiovascular disease risk. Women on thyroxine treatment were included if stable, as assessed by free T4 and thyroid stimulating hormone concentrations, and their dose had not changed in the 3 mo before study entry. Exclusion criteria: Planned frequent trips or long periods abroad that would result in an increased exposure to UVB light, or an abnormal biochemical profile on screening. N participants randomised/completed/analysed G1: 102/90/ITT 90, PP 88 G2: 102/85/ITT 84, PP 84 G3: 101/90/ITT 90, PP 88	Sex: Females Age (y) G1: 64.6 ± 2.3 G2: 64.2 ± 1.9 G3: 64.9 ± 2.2 Serum 25(OH)D (nmol/L) G1: 35.8 ± 16.4 G2: 33.4 ± 13.2 G3: 33.2 ± 13.8 BMI (kg/m2) G1: 25.9 ± 3.8 G2: 25.3 ± 3.9 G3: 25.2 ± 3.4 Ethnicity: White Smoking status: Non‐smokers Alcohol use: NR Health status: Healthy Season: Jan–March at baseline.	Vitamin D3 Doses [labeled] G1: placebo G2: vitamin D3 400 IU/d [10 μg/d] G3: vitamin D3 1000 IU/d [25 μg/d] Analysed doses G2: 346 IU [8.65 μg/d] G3: 832 IU [20.8 μg/d] Background vitamin D intake (μg/d) G1: 5.6 ± 3.0 G2: 4.6 ± 2.5 G3: 5.3 ± 2.9 Background calcium intake (mg/d) G1: 1291 ± 492 G2: 1261 ± 488 G3: 1306 ± 568 Compliance Pill count method (%) All: 92 on average (range 72–98) Serum 25(OH)D at 1 yr (nmol/L) G1: 32.0 ± 1.6 G2: 65.0 ± 2.1 G3: 76.0 ± 2.0 reported as mean ± SEM	Fractures ‐ reported as adverse events. **** Assay of serum 25(OH)D: LC–MS/MS	Data extracted: unclear ≥ 1 fracture, n of participants G1: 3 G2: 3 G3: 0 There were 7 fractures during the study, with one woman having two fractures on two separate occasions: ‐ wrist/lower arm, n = 3 ‐ foot/ankle, n = 3 ‐ clavicle, n = 1	1
Peacock et al. (2000) USA, Indiana Latitude [assumed] 42.74° N 4 y Public funding	RCT (parallel) Inclusion criteria: Women and men aged 60 and over. Exclusion criteria: A terminal illness; Paget's disease of bone; recurrent urinary stone disease; had been treated with sodium fluoride, bisphosphonate, steroids, or dilantin; renal disease requiring specific treatment; or excluded by their primary physician. N participants Randomised: All: 437 Completed: All: 236 Baseline information available7): Females G1: 98 G2: 89 G3: 95 Male G1: 37 G2: 37 G3: 37 7) those who had measurement of bone mineral density at femoral neck, total hip, or lumbar spine and were studied at least one visit after baseline.	Sex (% females) G1: 73 G2: 71 G3: 72 Age (y) Females G1: 72.3 ± 7.5 G2: 73.9 ± 8.0 G3: 74.1 ± 8.3 Male G1: 75.4 ± 7.6 G2: 76.0 ± 7.7 G3: 75.5 ± 7.2 Serum 25(OH)D (nmol/L) Females G1: 60.0 ± 30 G2: 62.5 ± 25 G3: 57.5 ± 33 Male G1: 65.0 ± 30 G2: 67.5 ± 23 G3: 65.0 ± 25 BMI: NR Ethnicity: White Smoking status: NR Alcohol use: NR Health status: NR Season: NR	Calcidiol Doses [labeled] G1: placebo G2: calcium 750 mg/d G3: calcidiol 15 μg/d Analysed doses: Capsules analysed every 6 mo; no significant decrease observed over 4 y. Background vitamin D intake: NR Background calcium intake (mg/d) Females G1: 586 ± 290 G2: 564 ± 294 G3: 572 ± 267 Male G1: 629 ± 249 G2: 670 ± 325 G3: 739 ± 335 Compliance Pill count method – calcidiol capsules at each visit (%) All: 89 ± 16 Pill count method – calcium tablets at each visit (%) All: 80 ± 20 Pill count method – placebo capsules at each visit (%): All: 85 ± 19 Serum 25(OH)D at the endpoint: NR	Fractures ‐ vertebral fractures: defined as a reduction of the anterior vertebral height of 20% or greater ‐ obtained from diaries kept by the participants ‐ were recorded at each visit along with the type of trauma responsible, whether the fracture was confirmed by radiography, and whether it required splinting or surgery. ‐ the occurrence of vertebral fractures from L4 to T4 was assessed from lateral thoracic and lumbar radiographs taken at the first and last visit for each subject. **** Assay of serum 25(OH)D: CPBA (vitamin D‐binding protein from rat serum) after HPLC	Data extracted: unclear Fractures Nonvertebral fractures over 4 y, n of events Females G1: 9 G2: 9 G3: 10 Male G1: 1 G2: 2 G3: 4 Vertebral fractures over 4 y, n of events Females G1: 10 G2: 5 G3: 15 Male G1: 3 G2: 2 G3: 4 Total fractures over 4 y, n of events Females G1: 19 G2: 14 G3: 25 Male G1: 4 G2: 4 G3: 8	1
Prince et al. (2008) Australia Latitude 32° S 1 yr Public funding	RCT (parallel) Inclusion criteria: Women aged 70–90 years, with a history of falling in the past 12 months with a plasma 25(OH)D concentration < 24.0 ng/mL [< 60 nmol/L]. Exclusion criteria: Current vitamin D consumption; current consumption of bone or mineral active agents apart from calcium; a bone mineral density z score at the total hip site of less than −2.0; medical conditions or disorders that influence bone mineral metabolism, including laboratory evidence of renal insufficiency (a creatinine level more than 2‐fold above the reference range); a fracture in the past 6 months; a Mini‐Mental State Examination score of <24; or the presence of marked neurological conditions likely to substantially impair balance or physical activity, such as stroke and Parkinson disease. N participants randomised/completed/analysed G1: 151/131/ ITT 151 G2: 151/124/ ITT 151	Sex: Females Age (y) G1: 77.4 ± 5.0 G2: 77.0 ± 4.2 Serum 25(OH)D (ng/mL) G1: 17.7 ± 5.1 ng/mL [44.3 ± 12.8 nmol/L] G2: 18.1 ± 5.0 ng/mL [45.3 ± 12.5 nmol/L] BMI: NR Ethnicity: NR Smoking status: NR Alcohol use: NR Health status: NR Number of falls in the past 12 mo (%) 1: G1: 57.6 G2: 59.6 2: G1: 26.5 G2: 27.2 3: G1: 13.2 G2: 9.9 > 3: G1: 2.6 G2: 3.3 Season: Recruitment from Apr 2003 to Oct 2004.	Vitamin D2 Doses G1: placebo + calcium 1000 mg/d G2: vitamin D2 1000 IU/d [25 μg/d] + calcium 1000 mg/d. Background vitamin D intake: NR Background calcium intake (mg/d) G1: 1080 ± 426 G2: 1067 ± 484 Compliance Pill count method (%) G1: 86 G2: 86 Serum 25(OH)D in winter/spring G2 vs. G1: 28.1% higher. Serum 25(OH)D in summer/autumn G2 vs. G1: 12.5% higher.	Fractures ‐ reported as adverse events. Falls ‐ defined as unintentionally coming to rest on the ground, floor, or other lower level ‐ obtained by interviewing participants every 6 wk; the number of falls that had occurred in the previous 6 weeks and the associated features of the falls were recorded on a falls questionnaire. **** Assay of serum 25(OH)D: RIA (Dia‐Sorin, Stillwater, Minnesota)	Data extracted: ITT Fractures Fractures over 1 yr, rate (%) G1: 2.0 G2: 2.6 Falls ≥ 1 fall, n of participants G1: 95 G2: 80 1 fall, OR (95% CI) G2 vs G1: 0.50 (0.28, 0.88) ≥ 1 fall, OR (95% CI) G2 vs G1: 0.66 (0.41, 1.06) ≥ 1 fall adjusted for baseline height, OR (95% CI) G2 vs G1: 0.61 (0.37, 0.99) ≥ 2 falls, OR (95% CI) G2 vs G1: 0.86 (0.50, 1.49) First fall in summer/autumn, OR (95% CI) G2 vs G1: 0.81 (0.46, 1.42) First fall in winter/spring, OR (95% CI) G2 vs G1: 0.55 (0.32, 0.96) First fall in winter/spring, RR (95% CI) G2 vs G1: 0.77 (0.56, 0.98)	2
Smith et al. (2017) (Earlier publication by Gallagher et al. 2012 was used for baseline information) ViDOS USA Latitude 41° N 1 yr Mixed funding	RCT (parallel) Inclusion criteria: Healthy, white, postmenopausal women aged 57 to 90 years who were at least 7 years postmenopausal (determined from the history of their last menstrual period) with vitamin D insufficiency Exclusion criteria: Significant health problems, active nephrolithiasis or history of more than two kidney stones in their lifetime, chronic renal failure (serum creatinine >1.4 mg/dL), chronic liver disease, medical conditions severe enough to prevent reasonable physical activity, serum 25(OH)D levels <5 ng/mL (12.5 nmol/L), serum calcium levels of 10.3 mg/dL (2.575 mmol/L) or more or serum calcium levels more than 0.3 mg/dL higher than the upper normal limit on two baseline tests, and 24‐h urine calcium levels >300 mg/dL (7.5 mmol) on two baseline tests; taking currently bisphosphonates or had taken them for >3 months in the past were excluded; use of fluoride, parathyroid hormone (PTH) or its derivatives, calcitonin, estrogen (in the last 6 mo), corticosteroids (>10 mg/d), phenytoin or phenobarbital, or high‐dose thiazide (>37.5 mg/d); multivitamins containing vitamin D were not allowed in the study. N participants, randomised/completed/analysed G1: 21/18/19 G2: 20/16/18 G3: 21/17/18 G4: 20/19/19 G5: 21/20/19 G6: 20/18/18 G7: 20/16/17 G8: 20/18/18 [Number of completed participants and their baseline characteristics obtained from the earlier publication the study referred to (Gallagher et al. 2012)]	Sex: Females Age (y) G1: 66 ± 6.5 G2: 68 ± 8.6 G3: 68 ± 8.1 G4: 66 ± 7.4 G5: 66 ± 6.3 G6: 69 ± 7.7 G7: 66 ± 7.1 G8: 65 ± 6.1 Serum 25(OH)D (nmol/L) G1: 37.7 ± 9.1 G2: 37.8 ± 10.8 G3: 39.0 ± 9.5 G4: 37.4 ± 10.2 G5: 38.2 ± 10.1 G6: 39.8 ± 8.2 G7: 37.2 ± 9.2 G8: 38.6 ± 9.1 BMI (kg/m2) G1: 31.1 ± 5.2 G2: 30.3 ± 5.4 G3: 28.2 ± 6.1 G4: 30.0 ± 5.4 G5: 30.4 ± 5.4 G6: 30.2 ± 5.7 G7: 29.7 ± 6.4 G8: 32.1 ± 6.2 Ethnicity: White Smoking status (%) Current: G1: 19 G2: 10 G3: 5 G4: 20 G5: 5 G6: 15 G7: 0 G8: 10 Former: G1: 33 G2: 35 G3: 33 G4: 40 G5: 38 G6: 20 G7: 50 G8: 45 Never: G1: 48 G2: 55 G3: 62 G4: 40 G5: 57 G6: 65 G7: 50 G8: 45 Alcohol users (%) G1: 33 G2: 35 G3: 57 G4: 50 G5: 52 G6: 70 G7: 70 G8: 80 Health status: Healthy. Fallen in the previous 12 mo (%) Caucasian: 32.2 African American: 25.3 Season: Enrolment in winter and spring over 2 years: Apr to May 2007 and Jan to May 2008.	Vitamin D3 Doses G1: placebo + calcium G2: vitamin D3 400 IU/d [10 μg/d] + calcium G3: vitamin D3 800 IU/d [20 μg/d] + calcium G4: vitamin D3 1600 IU/d [40 μg/d] + calcium G5: vitamin D3 2400 IU/d [60 μg/d] + calcium G6: vitamin D3 3200 IU/d [80 μg/d] + calcium G7: vitamin D3 4000 IU/d [100 μg/d] + calcium G8: vitamin D3 4800 IU/d [120 μg/d] + calcium Calcium to maintain total intake between 1200 to 1400 mg/d (was based on a baseline 7‐day food diary) Background vitamin D intake (IU/d) G1: 105 ± 61 IU/d [2.6 ± 1.5 μg/d] G2: 98 ± 58 IU/d [2.5 ± 1.5 μg/d] G3: 135 ± 70 IU/d [3.4 ± 1.8 μg/d] G4: 125 ± 71 IU/d [3.1 ± 1.8 μg/d] G5: 98 ± 55 IU/d [2.5 ± 1.4 μg/d] G6: 109 ± 62 IU/d [2.7 ± 1.6 μg/d] G7: 106 ± 83 IU/d [2.7 ± 2.1 μg/d] G8: 137 ± 86 IU/d [3.4 ± 2.2 μg/d] Background calcium intake (mg/d) G1: 593 ± 182 G2: 606 ± 212 G3: 741 ± 247 G4: 754 ± 244 G5: 612 ± 190 G6: 725 ± 263 G7: 673 ± 324 G8: 768 ± 348 Compliance Pill count method ‐ vitamin D3 capsules (%) All: 94 on average Pill count method – calcium tablets (%) All: 91 on average Serum 25(OH)D at 1 yr: G1 vs. the other groups: levels were significantly lower (visual presentation).	Falls ‐ defined as a sudden unintentional change in position causing an individual to land on the ground, floor, or at a lower level, with or without injury ‐ details on the number of falls and whether a fall resulted in a break or fracture were collected by an interviewer every 3 mo. **** Assay of serum 25(OH)D: RIA (Diasorin kit) and LC–MS	Data extracted: unclear ≥ 1 fall over 1 yr, rate (%) G1: 58 G2–G3: 53 G4–G6: 30 G7–G8: 69 P = 0.030 for difference in rates between groups. Lower faller rate in G4–G6 vs the other groups, P < 0.05. Falls over 1 yr, mean ± SE 8) G1: 0.94 ± 0.23 G2–G3: 0.85 ± 0.19 G4–G6: 0.41 ± 0.09 G7–G8: 0.79 ± 0.19 P = 0.030 for difference between groups. In pairwise comparisons after adjusting for multiple comparisons fewer falls in G4–G6 vs G1, P = 0.058; G4–G6 vs G2–G3, P = 0.058; and G4–G6 vs G7–G8, P = 0.094. ≥ 1 fall, OR (95% CI) 9) G1 vs G4–G6: 3.86 (1.24, 12.04) G2–G3 vs G4–G6: 3.15 (1.24, 7.99) G7–G8 vs G4 –G6: 5.63 (2.14, 14.85) 8) predicted means; adjusted for age, BMI, smoking status and alcohol use. 9) adjusted for age, BMI, smoking status, alcohol use, and history of falls in the past 12 mo prior to the study. At 1 yr, the quadratic trend observed in faller rate was stronger for the quintiles of serum 25(OH)D concentrations measured by LC–MS than for those measured by RIA. By RIA, the highest faller rate of 72% was in the 4th quintile [range 38–45.9 ng/mL or 95–114.8 nmol/L]. By LC–MS, the highest faller rate of 68% was in the 1st quintile [<28 ng/mL or < 70 nmol/L].	2
Uusi‐Rasi et al. (2015) Finland Latitude [assumed] 61.5° N 2 y Mixed funding	RCT (parallel) Inclusion criteria: Home‐dwelling women 70–80 years, fallen at least once during the previous 12 mo, did not use vitamin D supplements, and had no contraindications to exercise. Exclusion criteria: Participating in moderate to vigorous exercise >2 h/wk; regular use of vitamin D or calcium + vitamin D supplements; a recent fracture (during preceding 12 months); a marked decline in the basic activities of daily living (ADL); cognitive impairments (Mini Mental State Examination, MMSE‐test); primary hyperthyroidism; and degenerative conditions, such as Parkinson's disease. N participants randomised/completed/analysed G1: 102/95/102 G2: 103/91/103 G3: 102/88/102 G4: 102/96/102	Sex: Females Age (y) G1: 73.8 ± 3.1 G2: 74.8 ± 2.9 G3: 74.1 ± 3.0 G4: 74.1 ± 2.9 Serum 25(OH)D (ng/mL) G1: 27.1 ± 7.5 ng/mL [67.8 ± 18.8 nmol/L] G2: 27.8 ± 7.2 ng/mL [69.5 ± 18.0 nmol/L] G3: 26.4 ± 6.9 ng/mL [66.0 ± 17.3 nmol/L] G4: 26.2 ± 7.0 ng/mL [65.5 ± 17.5 nmol/L] BMI: NR Ethnicity [assumed]: Majority Caucasian Smoking status: 13 women were current smokers. Alcohol use: Stated to be low. Health status (%) Hypertension: G1: 41 G2: 35 G3: 51 G4: 52 Cardiovascular disease: G1: 18 G2: 20 G3: 16 G4: 16 Hypothyroidism: G1: 19 G2: 24 G3: 17 G4: 26 Diabetes mellitus: G1: 8.8 G2: 9.7 G3: 12 G4: 5.8 Osteoarthitis: G1: 23 G2: 25 G3: 28 G4: 33 Depression: G1: 2.0 G2: 1.9 G3: 4.9 G4: 4.9 Season: April 2010 to March 2013.	Vitamin D3 Doses G1: placebo + no exercise G2: placebo + exercise G3: vitamin D3 800 IU/d [20 μg/d] + no exercise G4: vitamin D3 800 IU/d [20 μg/d] + exercise Exercise = supervised, progressive group training classes 2 times/wk for the first 12 mo and once/wk for the remaining 12 mo. Background vitamin D intake (μg/d) G1: 10.2 ± 4.1 G2: 10.3 ± 3.6 G3: 10.9 ± 4.2 G4: 10.4 ± 3.9 Background calcium intake (mg/d) G1: 1040 ± 345 G2: 1119 ± 346 G3: 1125 ± 420 G4: 1109 ± 385 Compliance Pill count method (%): All: 98.1 on average (range 42.6–100) Attendance at all offered training sessions (%): All: 72.8 on average (range 0–97.4) Serum 25(OH)D at 24 mo (ng/mL): G1–G2: 27.5 ± 6.9 ng/mL [68.8 ± 17.3 nmol/L] G3–G4: 37.0 ± 7.4 ng/mL [92.5 ± 18.5 nmol/L]	Falls ‐ defined as an unexpected event in which the participant comes to rest on the ground, floor or lower level ‐ obtained from prospective diaries that were returned monthly via mail; details of each fall ascertained by a phone call. Injurious falls ‐ defined as those for which participants sought medical care; included e.g. bruises or fractures. **** Assay of serum 25(OH)D: EIA (Octeia; IDS)	Data extracted: ITT Falls All falls, rate per 100 Person‐years G1: 118.2 G2: 120.7 G3: 132.1 G4: 113.1 All falls, IRR (95% CI) G2 vs G1: 1.07 (0.77, 1.45) G3 vs G1: 1.08 (0.78, 1.52) G4 vs G1: 0.99 (0.72, 1.39) Fallers, HR (95% CI) G2 vs G1: 0.93 (0.66, 1.31) G3 vs G1: 0.77 (0.54, 1.11) G4 vs G1: 0.91 (0.64, 1.28) Multiple fallers, HR (95% CI) G2 vs G1: 1.14 (0.76, 1.71) G3 vs G1: 1.07 (0.71, 1.62) G4 vs G1: 1.14 (0.77, 1.71) Injurious falls Injurious falls, rate per 100 Person‐years G1: 13.2 G2: 6.5 G3: 12.9 G4: 5.0 Injurious falls, IRR (95% CI) G2 vs G1: 0.46 (0.22, 0.95) G3 vs G1: 0.84 (0.45, 1.57) G4 vs G1: 0.38 (0.17, 0.81) Injured fallers, HR (95% CI) G2 vs G1: 0.47 (0.23, 0.99) G3 vs G1: 0.89 (0.47, 1.69) G4 vs G1: 0.38 (0.17, 0.83) Cumulative hazard presented.	1
Wood et al. (2014) United Kingdom Latitude 57° N 1 yr Mixed funding	RCT (parallel) Inclusion criteria: Healthy postmenopausal women aged 60–70 years, BMI 18–45 kg/m2. Exclusion criteria: Severe disease; taking vascular medications or dietary supplements known to contain vitamin D2 or D3; current smokers; participants with abnormal blood biochemistry at study screening. N participants randomised/completed/analysed G1: 102/91/100 G2: 102/84/97 G3: 101/90/96	Sex: Females Age (y) G1: 63.9 ± 2.3 G2: 63.5 ± 1.9 G3: 64.1 ± 2.3 Serum 25(OH)D (nmol/L) G1: 36.18 ± 17.1 G2: 32.74 ± 12.9 G3: 32.41 ± 13.8 BMI G1: 26.6 ± 4.4 G2: 26.6 ± 4.2 G3: 26.8 ± 4.2 Ethnicity: Caucasian Smoking status: Non‐smokers. Alcohol use: NR Health status: Relatively healthy. Fallen over the last 2 mo prior to the study (%) G1: 7 G2: 8 G3: 8 Season: Jan–March 2009 at baseline.	Vitamin D3 Doses [labeled] G1: placebo G2: vitamin D3 400 IU/d [10 μg/d] G3: vitamin D3 1000 IU/d [25 μg/d] Analysed doses G2: 346 IU [8.65 μg] G3: 832 IU [20.8 μg] Background vitamin D intake: NR Background calcium intake: NR Compliance Pill count method (%) All: >95% Serum 25(OH)D, change over 12 mo (nmol/L), mean (95% CI) G1: −2.72 (−5.15, −0.29) G2: +33.04 (29.03, 37.06) G3: +42.90 (39.09, 46.72)	Falls ‐ not defined ‐ recorded at each study visit by asking the question” Have you had any recent falls in the past 2 months?” **** Assay of serum 25(OH)D: MS/MS	Data extracted: ITT Falls over 12 mo, n of events G1: 40 G2: 48 G3: 30 ≥1 fall over 12 mo, n of participants G1: 31 G2: 33 G3: 27 P = 0.65 for difference in incidence between groups.	2

Abbreviations: BEST‐D: Biochemical Efficacy and Safety Trial of vitamin D; BMI: body mass index; CI: confidence interval; CLIA: chemiluminescence immunoassay; CPBA: competitive protein binding assay; CT: controlled trial; DO‐HEALTH: Vitamin D₃ ‐ Omega3 ‐ Home Exercise ‐ Healthy Ageing and Longevity Trial; EIA: enzyme immunoassay; G: group; HPLC–MS/MS: high‐performance liquid chromatography tandem mass spectrometry; HR: hazard ratio; IQR: inter quartile range; IRR: incidence rate ratio; ITT: intention‐to‐treat; LC–MS: liquid chromatography mass spectrometry; LC–MS/MS: liquid chromatography tandem mass spectrometry; MS/MS: tandem mass spectrometry; NA; not applicable; NR: not reported; OR: odds ratio; PP: per‐protocol; RECORD: Randomised Evaluation of Calcium Or vitamin D; RIA: radioimmunoassay; RCT: randomised controlled trial; RR: relative risk; SE; standard error; SEM; standard error of mean; STURDY: Study to Understand Fall Reduction and Vitamin D in You; ViDOS: Vitamin D supplementation in Older Subjects; VITAL: VITamin D and OmegA‐3 TriaL; 25(OH)D: 25‐hydroxyvitamin D.

^(a)the values have been reported as mean ± standard deviation or median (IQR) unless otherwise indicated; IQR = 25^th–75^th percentiles or the length between the percentiles.