Table 2.

Summary of included articles listed by year.

	Author Year Country Study Design	Population Characteristics	OI Type/Reported Severity/Genetic Testing	Vitamin D	Study Aim (s) and Main Results	Summary	Strength/ Limitation of the Study
1	Mohsenzade et al., 2021 [71] Iran Case control study	23 children affected by OI, 23 age–gender-matched controls; 9 males, 14 females	6 cases OI I 17 cases OI IV No molecular analysis data	Vitamin D deficiency was found in 43% of OI patients vs. 56% of controls Vitamin D levels were higher in OI patients (p = 0.033)	Aim: to assess the BMD and vitamin D level in children with OI in Iran Results: 43.4% of OI children had vitamin D deficiency No association between vitamin D levels and BMD parameters	Vitamin D deficiency is prevalent in OI patients.	Strength: -Case-control study assessing vitamin D status, BMD, and volumetric BMD in children Limitations: -Small sample -Self-reported data from a standard questionnaire -All the patients had received vitamin D supplements since the time of diagnosis
2	Nazim et al., 2019 [72] Egypt Case control study	26 children affected by OI, 26 controls; 13 males, 13 females in OI group	9 cases OI I 11 cases OI III 6 cases OI IV No molecular analysis data	25(OH) vitamin D lower than the reference range in 4 patients and > 100 µg/L in 5 cases. Note: In the study all patients were on vitamin D oral supplement	Aim: evaluate bone turnover markers in the Egyptian bone patients and the effect of bisphosphonate treatment in these markers Results: Serum calcium measurement, osteocalcin, P1NP are valuable for monitoring the effect of bisphosphonate treatment	4/26 patients showed low levels of vitamin D	Strengths: -Case-control study -Biochemical measurements, markers of bone formation, and markers of type I collagen degradation evaluation -Measurements at baseline, 6 months of treatment, and 12 months of treatment Limitations: -Small sample -Bisphosphonate treatment -Important variables not evaluated (number and location of fractures, Tanner stage, dietary vitamin D intake, and body composition)
3	Zambrano et al., 2016 [73] Brazil Cross-sectional study	52 patients affected by OI Age 1–19 y 29 females, 23 males	24 cases OI I 5 cases OI III 23 cases OI IV No molecular analysis data	Vitamin D deficiency was found in 35.5% and vitamin D insufficiency was found in 51.9% of OI patients; in 88.4% of cases vitamin D levels were insufficient or deficient	Aim: to assess the relationship between determinants of vitamin D status in pediatric patients with OI. Results: Vitamin D levels were insufficient or deficient in 88% of cases. Vitamin D levels were associated to LS- BMD z-score and were positive correlated to height. No significant difference in OI type No correlation with season of assessment No correlation with PTH or circulating bone markers was found	High prevalence of vitamin D low levels Correlation between vitamin D levels and LS BMD Z-score and height	Strengths: -Different outcomes assessed as vitamin D status, BMD, information about sun exposition, mobility, and bisphosphonate therapy Limitations: -Small sample -Blood samples collected in autumn/winter. -There are no longitudinal data -There are no data about vitamin D supplementation effects. -Important variables not reported (the number/location of fractures, Tanner stage, dietary vitamin D intake, and body composition)
4	Plante et al., 2016 [74] Canada Clinical randomized controlled trial.	60 individuals affected by OI Age 6 to 18.9 y; 35 females and 25 males Population was stratified for baseline bisphosphonate treatment and pubertal stage	23 cases OI 25 cases OI IV 12 cases OI III, V, or VI	Baseline vitamin D concentration, 80% > 50 nmol/L	Aim: to evaluate the efficacy of high-dose vitamin D supplementation on LS-aBMD in children with OI. Results: No significant differences in LS-aBMD z-score changes were detected between treatment groups Increase in vitamin D OH level after supplementation significantly higher in group receiving 2000 IU vitamin D	No significant differences in LS-aBMD z-score changes	Strengths: -Randomized controlled trial -Evaluation of vitamin D supplementation -Patients under bisphosphonate treatment in the previous 2 years were excluded Limitations: -No collected data reflecting endogenous vitamin D synthesis, such as skin pigmentation or sun exposure. -Simultaneous treatment with intravenous bisphosphonates in high proportion of participants
5	Wilsford et al., 2013 [75] USA Retrospective chart review	80 children with OI; charts of 44 children (26 female) had documentation of the variables of interest.	15 cases OI I 12 cases OI III 17 cases OI IV No molecular analysis data	Almost 80% of children with OI had insufficient or deficient levels of vitamin D	Aim: to evaluate the prevalence of vitamin D deficiency and possible risk factors influencing the vitamin D serum levels in patients with (OI). Results: Significant correlations with low vitamin D levels were found for older age (p < 0.001), African American descent (p = 0.01), BMI (p < 0.001), BMI percentile (p = 0.30), consumption of soda (p = 0.009), and pamidronate therapy (p = 0.004).	High prevalence of vitamin D deficiency or insufficient levels. Significant correlations with low vitamin D levels and BMI	Strengths: -Evaluation of several relevant parameters (season of year, level of ambulation, BMI, type of OI, time spent outdoors, and use of sunscreen before playing outdoors) Limitations: -Retrospective study -Missing number and location of fractures as main outcome. -Thirty-four (79.5%) patients had a history of pamidronate therapy
6	Chagas et al., 2012 [76] Brazil Cross-sectional study	26 patients affected by OI 13 type I OI and 13 type III OI 8 healthy controls Note: all patients were in treatment with pamidronate	13 cases OI I 13 cases OI III No molecular genetic testing information reported	69% type I patients 77% type III patients showed insufficient vitamin D levels 8% type III OI presented Vitamin D deficiency	Aim: Evaluate nutritional status, bone mineral density and biochemical parameters in OI subjects Results: in patients with OI number of fractures was positively related to body mass index and the percentage of body fat and negative correlated to lean body mass. Even taking dietary supplements, 12% of subjects did not achieve vitamin D recommendations	High prevalence of insufficient vitamin D levels in both type I and type III OI	Strengths: -Equal number of OI type 1 and type 3 patients. -First study in which a nutritional evaluation was performed in subjects with OI and body composition information collected. Limitations: -Small sample -Missing number and location of fractures as main outcome -No information about season -All patients were in treatment with pamidronate
7	Wekre et al., 2011 [77] Norway Case series	97 adult OI patients 41 males and 56 females Type I OI 74 Type III OI 9 Type IV OI 11 Unclassified 2	75 cases OI I 9 cases OI III 11 cases OI IV 2 unclassified cases No molecular analysis information	All patients showed normal levels of PTH, calcium and Vitamin D. OI type III displayed significantly lower values for 25 vitamin (OH) D (p = 0.05) than persons with type I and IV	Aim: Assess bone mass, bone turnover and prevalence of fractures in adult OI patients Results osteoporotic T scores in only 10% of patients Bone turnover markers were normal in the vast majority of patients. In adults with OI type III, bone turnover tended to be increased and osteoporosis more prevalent Seventeen persons (16 females and 1 male) were underbisphosphonates and/or hormone replacement therapy. There were no significant differences in anti-osteoporosis treatment between OI subtypes	Adults with OI type III, bone turnover tended to be increased, and osteoporosis more prevalent, and lower vitamin D levels than other OI types	Strengths: -Study in adult population -Prevalence and localization of fractures were evaluated Limitations: -Relatively small sample -Patient self-reported total number of fractures -No molecular analysis information -No information about bisphosphonate use in childhood -Other parameters (season, dietary vitamin D intake, sun exposure) not evaluated
8	Edouard et al. [78] 2011a Canada Retrospective study	71 patients affected with OI type I, III, or IV Age 1.4–17.5; 36 females, 35 males	29 cases OI I 12 cases OI III 30 cases OI IV In 63 patients a COL1A or COL2A3 mutation was identified (sequence analysis was performed in 65 patients)	Vitamin D deficiency in 52% of cases (Vitamin D concentration ≤ 50 nmol/L) Vitamin D concentration ≤ 80 nmol/L were found in 94% patients	Aim: to evaluated the relationship between vitamin D status and parameters of skeletal mineralization, mass, and metabolism in a group of pediatric osteogenesis imperfecta (OI) patients. Results: vitamin D was negative correlated with age and serum PTH levels No correlation with alkaline phosphatase levels. No seasonal variability Vitamin D levels were not related with bone formation rate, osteoid thickness, mineralization lag time. No evidence that vitamin D levels from 13 to 103 nmol/L were associated with measurement of bone mineralization, metabolism or mass in children with OI.	Deficient or low levels of vitamin D were found in more than 50% of patients Negative correlation between PTH levels and vitamin D levels was observed No seasonal variability	Strengths: -Histomorphometric parameters evaluated Limitations: -Small sample -Missing number and location of fractures as main outcome -No information about season or detailed information about treatment history
9	Edouard et al. [79] 2011b Canada Retrospective cross-sectional study	315 patients affected with OI type I, III, or IV Age 1.1–17.9 y; 161 females and 154 males	165 cases OI I 56 cases OI III 94 cases OI IV Collagen type I molecular testing available in 254 patients. Disease causing mutation in 222 patients	Vitamin D deficiency in 27% of cases Lowers levels in teenagers Levels decreased less markedly in winter than in other studies	Aim: evaluated vitamin D status determinants in children and adolescent OI patients Results: vitamin D levels were associated to LS-aBMD z-score in children and adolescents with OI, type I, III, IV. Vitamin D levels were inversely associated to PTH levels.	Vitamin D deficiency is prevalent in OI Lower levels of vitamin D were associated to LS-aBMD score and teenage.	Strengths: -Large sample size. -No previous treatment with bisphosphonate. Limitations: -No additional variables evaluated
10	Bowden et al., 2008 [80] USA Retrospective study	84 children with osteopenia or osteoporosis 24 OI patients (28% of the total)	There was no information about OI type or severity Some cases underwent collagen fibroblast analysis. No information about molecular genetics	Vitamin D deficiency was observed in 26% of OI cases Insufficient levels in 7% of OI patients	Aim: To determine the prevalence of vitamin D deficiency and insufficiency in children with osteopenia or osteoporosis and to evaluate the relationship between serum vitamin D levels and bone parameters, including bone mineral density. Results: A high prevalence of vitamin D insufficiency was found in this series of children with osteopenia or osteoporosis, regardless of the etiology of bone disorder. Negative correlation between vitamin D levels and PTH levels. No effect of seasonality on vitamin D.	High prevalence of insufficient or deficient vitamin D levels. Negative correlation between Vitamin D levels and PTH levels No effect of seasonality on vitamin D	Strengths: -Data about fracture rate concurrent with drug therapy -Demographic data, and -detailed medical history and biochemical laboratory studies Limitations: -Relatively small sample -Other disease with bone fragility included. -Other important variables not reported (i.e., type of OI or OI severity, location of fractures, season)