Low-energy fractures, also termed fragility fractures, are fractures resulting from trauma equivalent to a fall from standing height or less. Such fractures commonly involve the hip, vertebrae, distal radius and proximal humerus and represent an important clinical manifestation of impaired bone strength. Their occurrence is associated with pain, disability, loss of independence, recurrent fractures and increased healthcare burden. A low-energy fracture may be the first indication of underlying osteoporosis; therefore, affected patients require comprehensive evaluation of bone health and future fracture risk. Vitamin D plays a central role in calcium and phosphate homeostasis, intestinal calcium absorption, skeletal mineralisation and maintenance of neuromuscular function. Vitamin D deficiency can cause secondary hyperparathyroidism, increased bone turnover, bone loss and osteomalacia. It may also contribute to muscle weakness and falls, thereby increasing fracture susceptibility through skeletal and extraskeletal pathways [1,2]. Serum 25-hydroxyvitamin D [25(OH)D] is considered the most appropriate biochemical indicator of vitamin D status. Vitamin D deficiency is common among older adults, institutionalised individuals, postmenopausal women and patients presenting with fragility fractures. Bone mineral density (BMD), generally measured by dual-energy X-ray absorptiometry (DXA), is an established indicator of bone strength. According to standard diagnostic criteria, a T-score of -2.5 or below at the lumbar spine, femoral neck or total hip indicates osteoporosis, while a T-score between -1.0 and -2.5 indicates osteopenia. However, BMD alone does not capture all determinants of skeletal fragility, and fractures may also occur among individuals whose BMD lies within the osteopenic range [3]. The Fracture Risk Assessment Tool (FRAX) integrates clinical risk factors, with or without femoral-neck BMD, to estimate the 10-year probability of major osteoporotic fracture and hip fracture [4]. Clinical factors incorporated in FRAX include age, sex, body mass index, previous fracture, parental hip fracture, smoking, glucocorticoid exposure, rheumatoid arthritis, secondary osteoporosis and alcohol consumption. The combined assessment of vitamin D status, BMD and FRAX probability may consequently provide a more comprehensive evaluation than any individual parameter. Although vitamin D deficiency, reduced BMD and elevated fracture probability frequently coexist, their interrelationships among patients who have already sustained low-energy fractures remain clinically important. Identifying these relationships may help detect metabolic bone disease, stratify the probability of subsequent fractures and guide vitamin D correction, osteoporosis treatment and fall-prevention measures [3,5]. The present study therefore evaluated vitamin D status, BMD and estimated fracture risk among patients presenting with low-energy fractures. AIM To assess the relationship between serum vitamin D status, bone mineral density and estimated fracture risk among patients with low-energy fractures. OBJECTIVES 1. To determine serum 25-hydroxyvitamin D status among patients presenting with low-energy fractures. 2. To assess BMD at the lumbar spine and hip and classify participants as having normal BMD, osteopenia or osteoporosis. 3. To examine the association of vitamin D status and BMD with the estimated 10-year probability of major osteoporotic and hip fractures.

Source of Data The study data were obtained from adult patients presenting with radiologically confirmed low-energy fractures to the Orthopaedics Department. Participants were recruited from the orthopaedic outpatient department, emergency department and inpatient wards. Clinical information was supplemented by hospital records, radiological findings, biochemical investigations, DXA reports and structured participant interviews. Study Design This was a hospital-based, observational, analytical cross-sectional study. Study Location The study was conducted in the Department of Orthopaedics in collaboration with the Departments of Biochemistry and Radiodiagnosis. Study Duration The study was conducted over 18 months, including participant recruitment, biochemical evaluation, BMD assessment, data entry and statistical analysis. Study Population The study population consisted of eligible adult patients with a low-energy fracture who attended the selected hospital during the study period. A low-energy fracture was operationally defined as a fracture caused by a fall from standing height or less, or an equivalent minor trauma that would not ordinarily result in fracture in healthy bone. Sample Size The sample size was calculated using the single-population-proportion formula: n = (Zα/2)² × p(1-p) / d². At a 95% confidence level, Zα/2 was 1.96. Because a reliable prior prevalence estimate for the target hospital population was not available, p was taken as 0.50 to provide the maximum required sample size, and the absolute precision (d) was set at 0.07. Thus, n = (1.96² × 0.50 × 0.50) / 0.07² = 196. The sample size was rounded upward, and 200 eligible patients were included. Participants were recruited consecutively until the required sample size was achieved. Inclusion Criteria • Patients aged 40–90 years. • Male and female patients with a radiologically confirmed low-energy fracture. • Fractures resulting from a fall from standing height or less or equivalent minor trauma. • Patients who were clinically stable enough to undergo biochemical investigations and DXA assessment. • Patients who provided written informed consent. • Patients for whom the information required to calculate FRAX probability was available. Exclusion Criteria • Fractures caused by high-energy trauma, including road-traffic accidents, falls from substantial height or industrial injuries. • Pathological fractures due to primary bone tumours, skeletal metastases or other focal bone lesions. • Patients with severe chronic kidney disease, advanced chronic liver disease or malabsorption disorders likely to markedly alter vitamin D metabolism. • Patients with known hyperparathyroidism, untreated hyperthyroidism, osteomalacia of established non-vitamin D origin or other major metabolic bone disorders. • Patients receiving long-term anti-osteoporotic treatment before enrolment, when such treatment could substantially alter BMD. • Patients who had received pharmacological-dose vitamin D shortly before testing. • Pregnant or lactating women. • Patients with metallic implants or clinical conditions that prevented reliable DXA assessment at both principal sites. • Patients who refused consent or had incomplete essential clinical, biochemical or DXA data. Procedure and Methodology Approval was obtained from the Institutional Ethics Committee before commencement of the study. Written informed consent was obtained from every participant. Eligible patients were enrolled through consecutive sampling. Demographic information, including age, sex, residence, occupation and socioeconomic characteristics, was recorded using a predesigned case-record form. Height was measured to the nearest 0.1 cm, weight to the nearest 0.1 kg and body mass index was calculated as weight in kilograms divided by height in metres squared. A detailed history was obtained regarding the mechanism and site of the current fracture, previous fragility fractures, falls during the preceding year, parental history of hip fracture, smoking, alcohol consumption, physical activity, dietary calcium intake, sunlight exposure and use of vitamin D or calcium supplements. Information regarding menopause, glucocorticoid use, rheumatoid arthritis and diseases associated with secondary osteoporosis was also documented. The type and anatomical location of the fracture were confirmed from clinical and radiological records. Serum 25(OH)D was measured and categorised according to the prespecified laboratory criteria as: • Vitamin D deficiency: <20 ng/mL • Vitamin D insufficiency: 20–<30 ng/mL • Vitamin D sufficiency: ≥30 ng/mL BMD was measured using DXA at the lumbar spine (L1–L4), femoral neck and total hip. The lowest valid T-score was used for diagnostic classification in postmenopausal women and men aged 50 years or older: • Normal BMD: T-score ≥-1.0 • Osteopenia: T-score between -1.0 and -2.5 • Osteoporosis: T-score ≤-2.5 For premenopausal women and men younger than 50 years, Z-scores were interpreted, and a Z-score ≤-2.0 was considered “below the expected range for age.” The country-specific FRAX algorithm was used for patients aged 40–90 years. Age, sex, height, weight and clinical risk factors were entered into the tool. Femoral-neck BMD was included when available. The 10-year probabilities of major osteoporotic fracture and hip fracture were recorded as percentages. Because the participants already had a fracture, FRAX values were interpreted as estimates of subsequent fracture probability rather than as diagnostic confirmation of the index fracture. Sample Processing Approximately 5 mL of venous blood was collected from each participant under aseptic precautions into a plain serum-separator tube. The sample was allowed to clot and was centrifuged at approximately 3,000 revolutions per minute for 10 minutes. The separated serum was analysed promptly or stored at -20°C, according to the laboratory protocol, until analysis. Serum 25(OH)D was measured using the assay available in the institutional laboratory, such as chemiluminescent immunoassay or electrochemiluminescence immunoassay. Serum calcium, phosphorus, alkaline phosphatase, albumin and creatinine were measured using standard automated biochemical methods. Corrected serum calcium was calculated when required. All investigations were performed in accordance with the manufacturer’s instructions and internal laboratory quality-control procedures. Haemolysed, insufficient or improperly labelled specimens were rejected and recollected where feasible. Statistical Methods Data were entered into Microsoft Excel and analysed using SPSS 28.0. Continuous variables were examined for normality using histograms and the Shapiro–Wilk test. Normally distributed variables were presented as mean and standard deviation, whereas skewed variables were presented as median and interquartile range. Categorical variables were expressed as frequencies and percentages. Vitamin D levels, BMD values and FRAX probabilities were compared across relevant demographic and clinical groups using the independent-samples t test, one-way ANOVA or their non-parametric equivalents. The chi-square test or Fisher’s exact test was used to evaluate associations between categorical vitamin D and BMD groups. Pearson’s correlation coefficient was used for normally distributed continuous variables, and Spearman’s rank correlation was used for skewed or ordinal variables. A univariable linear regression model was fitted with the lowest BMD T-score as the dependent variable and serum 25(OH)D concentration as the predictor. The regression results were reported as the unstandardized coefficient (β), standard error, standardized β, 95% confidence interval, t value and p value; model fit was summarised using R², adjusted R² and the F statistic. All tests were two-sided, and p<0.05 was considered statistically significant. Data Collection Data were collected using a pretested, structured case-record form. Information was obtained through participant interviews, physical examination, review of medical and radiological records, serum biochemical investigations, DXA measurements and FRAX calculation. Each participant was assigned a unique study identification number. The investigator checked the forms for completeness and consistency on the day of data collection. Data were entered into a password-protected database and verified through random source-document checks and double-checking of entered values. Participants’ identities were removed from the analytical dataset, and all information was maintained confidentially. Missing data were documented, and participants without essential vitamin D, BMD or fracture-risk information were excluded from the relevant complete-case analysis

Table 1: Overall relationship between serum vitamin D, BMD and estimated fracture risk among patients with low-energy fractures (N=200) Parameter Value, Mean (SD) or n (%) 95% CI Test of significance P value Serum 25(OH)D, ng/mL 18.74 (8.63) 17.54–19.94 One-sample t=-18.45† <0.001* Lowest BMD T-score -2.36 (0.91) -2.49 to -2.23 One-sample t=2.18‡ 0.031* Major osteoporotic fracture probability, % 18.21 (9.47) 16.89–19.53 One-sample t=12.26§ <0.001* Hip-fracture probability, % 8.03 (6.12) 7.18–8.88 One-sample t=9.31¶ <0.001* Vitamin D deficiency, <20 ng/mL 111 (55.5%) 48.6%–62.2% Proportion z=1.56 0.120 Osteopenia or osteoporosis 161 (80.5%) 74.5%–85.4% Proportion z=8.63 <0.001* Osteoporosis 67 (33.5%) 27.3%–40.3% Proportion z=-4.67 <0.001* Serum 25(OH)D versus lowest BMD T-score r=0.42 0.30–0.53 Pearson t=6.51 <0.001* Serum 25(OH)D versus major osteoporotic-fracture probability r=-0.36 -0.48 to -0.23 Pearson t=-5.43 <0.001* Serum 25(OH)D versus hip-fracture probability r=-0.39 -0.50 to -0.27 Pearson t=-5.96 <0.001* Lowest BMD T-score versus major osteoporotic-fracture probability r=-0.57 -0.66 to -0.47 Pearson t=-9.76 <0.001* Lowest BMD T-score versus hip-fracture probability r=-0.62 -0.70 to -0.53 Pearson t=-11.12 <0.001* *Statistically significant at p<0.05. †Compared with the vitamin D sufficiency threshold of 30 ng/mL. ‡Compared with a reference T-score of -2.50. §Compared with a reference probability of 10%. ¶Compared with a reference probability of 4%. Table 1 presents the overall relationship between serum vitamin D, BMD and estimated fracture risk among 200 patients with low-energy fractures. The mean serum 25(OH)D concentration was 18.74±8.63 ng/mL (95% CI: 17.54–19.94), which was significantly below the vitamin D sufficiency threshold of 30 ng/mL (t=-18.45, p<0.001). The mean lowest BMD T-score was -2.36±0.91 (95% CI: -2.49 to -2.23), differing significantly from the reference threshold of -2.50 (t=2.18, p=0.031). The estimated mean 10-year probabilities of major osteoporotic fracture and hip fracture were 18.21±9.47% and 8.03±6.12%, respectively; both were significantly greater than their specified reference probabilities (p<0.001). Vitamin D deficiency was present in 111 (55.5%) patients, although this proportion did not differ significantly from 50% (z=1.56, p=0.120). Low BMD was highly prevalent, with 161 (80.5%) patients having osteopenia or osteoporosis (95% CI: 74.5%–85.4%; z=8.63, p<0.001), including 67 (33.5%) with osteoporosis. Serum 25(OH)D showed a significant moderate positive correlation with the lowest BMD T-score (r=0.42; 95% CI: 0.30–0.53; p<0.001), indicating that higher vitamin D concentrations were associated with better BMD. Conversely, vitamin D was inversely correlated with the probabilities of major osteoporotic fracture (r=-0.36; p<0.001) and hip fracture (r=-0.39; p<0.001). The lowest BMD T-score demonstrated stronger inverse correlations with major osteoporotic-fracture probability (r=-0.57; p<0.001) and hip-fracture probability (r=-0.62; p<0.001). Table 2: Serum 25-hydroxyvitamin D status among patients with low-energy fractures (N=200) Vitamin D parameter n (%) or Mean (SD) 95% CI Test of significance P value Serum 25(OH)D, ng/mL 18.74 (8.63) 17.54–19.94 One-sample t=-18.45† <0.001* Vitamin D deficient, <20 ng/mL 111 (55.5%) 48.6%–62.2% Vitamin D insufficient, 20–<30 ng/mL 58 (29.0%) 23.2%–35.6% χ²=49.69‡ <0.001* Vitamin D sufficient, ≥30 ng/mL 31 (15.5%) 11.1%–21.2% Vitamin D below 30 ng/mL 169 (84.5%) 78.8%–88.9% Proportion z=9.76 <0.001* Serum calcium, mg/dL 9.18 (0.47) 9.11–9.25 One-sample t=-0.60§ 0.549 Corrected serum calcium, mg/dL 8.81 (0.62) 8.72–8.90 One-sample t=-2.05§ 0.042* Serum phosphorus, mg/dL 3.41 (0.61) 3.32–3.50 One-sample t=-2.09¶ 0.038* Alkaline phosphatase, IU/L 126.8 (48.7) 120.01–133.59 One-sample t=7.78# <0.001* Vitamin D concentration according to fracture site Fracture site Number, n (%) Serum 25(OH)D, Mean (SD), ng/mL 95% CI of mean Test of significance P value Hip/proximal femur 63 (31.5%) 15.62 (7.44) 13.75–17.49 Distal radius 86 (43.0%) 20.41 (8.71) 18.54–22.28 ANOVA F=6.46 0.002* Vertebral/proximal humerus/other 51 (25.5%) 19.37 (8.26) 17.05–21.69 *Statistically significant at p<0.05. †Compared with 30 ng/mL. ‡Overall chi-square goodness-of-fit test for the three vitamin D categories. §Compared with the midpoint of the institutional reference range, 9.2 mg/dL. ¶Compared with 3.5 mg/dL. #Compared with 100 IU/L. Table 2 describes serum 25-hydroxyvitamin D status and associated biochemical measurements. The mean serum 25(OH)D concentration was 18.74±8.63 ng/mL (95% CI: 17.54–19.94), which was significantly below 30 ng/mL (t=-18.45, p<0.001). Vitamin D deficiency was identified in 111 (55.5%) patients, insufficiency in 58 (29.0%) and sufficiency in only 31 (15.5%). The distribution across these three categories differed significantly (χ²=49.69, p<0.001). Overall, 169 (84.5%) patients had serum vitamin D below 30 ng/mL (95% CI: 78.8%–88.9%), a proportion significantly greater than 50% (z=9.76, p<0.001). The mean serum calcium was 9.18±0.47 mg/dL and did not differ significantly from the reference value of 9.2 mg/dL (t=-0.60, p=0.549). However, corrected serum calcium was 8.81±0.62 mg/dL, which was significantly lower than the selected reference value (t=-2.05, p=0.042). Mean serum phosphorus was also slightly but significantly lower than the reference value at 3.41±0.61 mg/dL (t=-2.09, p=0.038). The mean alkaline phosphatase level was 126.8±48.7 IU/L and was significantly higher than 100 IU/L (t=7.78, p<0.001), potentially indicating increased bone turnover in a proportion of patients. Vitamin D concentrations also differed significantly according to fracture site (F=6.46, p=0.002). The lowest mean concentration occurred among 63 patients with hip or proximal-femur fractures at 15.62±7.44 ng/mL. It was higher among 86 patients with distal-radius fractures at 20.41±8.71 ng/mL and among 51 patients with vertebral, proximal-humerus or other fractures at 19.37±8.26 ng/mL. Table 3: BMD at the lumbar spine and hip and classification of patients according to BMD (N=200) A. Site-specific BMD measurements DXA measurement Mean (SD) 95% CI Test of significance P value Lumbar-spine BMD, g/cm² 0.82 (0.14) 0.80–0.84 One-sample t=-18.18† <0.001* Lumbar-spine T-score -2.31 (1.04) -2.46 to -2.16 One-sample t=2.58‡ 0.011* Femoral-neck BMD, g/cm² 0.67 (0.12) 0.65–0.69 One-sample t=-21.21† <0.001* Femoral-neck T-score -2.48 (1.11) -2.63 to -2.33 One-sample t=0.25‡ 0.799 Total-hip BMD, g/cm² 0.73 (0.13) 0.71–0.75 One-sample t=-18.48† <0.001* Total-hip T-score -2.12 (0.94) -2.25 to -1.99 One-sample t=5.72‡ <0.001* Lowest BMD T-score -2.36 (0.91) -2.49 to -2.23 Repeated-measures F=12.84§ <0.001* B. Classification according to the lowest valid T-score BMD classification n (%) 95% CI Test of significance P value Normal BMD, T-score ≥-1.0 39 (19.5%) 14.6%–25.5% Osteopenia, T-score between -1.0 and -2.5 94 (47.0%) 40.2%–53.9% χ²=22.69¶ <0.001* Osteoporosis, T-score ≤-2.5 67 (33.5%) 27.3%–40.3% Low BMD: osteopenia or osteoporosis 161 (80.5%) 74.5%–85.4% Proportion z=8.63# <0.001* *Statistically significant at p<0.05. †Compared with a reference BMD of 1.00 g/cm². ‡Compared with the osteoporosis threshold of -2.50. §Repeated-measures ANOVA comparing T-scores at the lumbar spine, femoral neck and total hip. ¶Chi-square goodness-of-fit test comparing the three diagnostic categories. #Compared with an expected proportion of 50%. Table 3 presents site-specific DXA measurements and classification according to the lowest valid BMD T-score. The mean lumbar-spine BMD was 0.82±0.14 g/cm², with a corresponding mean T-score of -2.31±1.04. Both values differed significantly from their respective reference values (p<0.001 and p=0.011, respectively). Femoral-neck BMD was the lowest among the measured sites at 0.67±0.12 g/cm², and its mean T-score was -2.48±1.11. Although femoral-neck BMD was significantly below 1.00 g/cm² (t=-21.21, p<0.001), its mean T-score did not differ significantly from the osteoporosis threshold of -2.50 (t=0.25, p=0.799), indicating that the group mean was close to this diagnostic threshold. The mean total-hip BMD was 0.73±0.13 g/cm², and the corresponding T-score was -2.12±0.94; both differed significantly from their reference values (p<0.001). The mean lowest T-score across the assessed skeletal sites was -2.36±0.91. Repeated-measures analysis demonstrated a significant difference among lumbar-spine, femoral-neck and total-hip T-scores (F=12.84, p<0.001). Based on the lowest valid T-score, 39 (19.5%) patients had normal BMD, 94 (47.0%) had osteopenia and 67 (33.5%) had osteoporosis. The distribution of patients across these categories was statistically significant (χ²=22.69, p<0.001). Overall, 161 (80.5%) patients had low BMD in the form of either osteopenia or osteoporosis (95% CI: 74.5%–85.4%), which was significantly higher than the reference proportion of 50% (z=8.63, p<0.001). These results demonstrate a substantial burden of impaired bone density among patients with low-energy fractures, with the femoral neck being the most severely affected skeletal site. Table 4: Association of vitamin D status and BMD with estimated 10-year fracture probability (N=200) A. Fracture probability according to vitamin D status Vitamin D status n Major osteoporotic-fracture probability, Mean (SD), % 95% CI Hip-fracture probability, Mean (SD), % 95% CI Deficient, <20 ng/mL 111 20.84 (8.16) 19.30–22.38 9.63 (5.29) 8.63–10.63 Insufficient, 20–<30 ng/mL 58 16.27 (6.74) 14.50–18.04 6.91 (4.18) 5.81–8.01 Sufficient, ≥30 ng/mL 31 12.43 (5.38) 10.46–14.40 4.37 (3.12) 3.23–5.51 Test of significance ANOVA F=18.47 ANOVA F=17.42 P value <0.001* <0.001* Table 4A demonstrates a progressive reduction in estimated fracture probability with improvement in vitamin D status. Patients with vitamin D deficiency had the highest mean 10-year major osteoporotic-fracture probability at 20.84±8.16%, followed by patients with vitamin D insufficiency at 16.27±6.74% and those with sufficient vitamin D at 12.43±5.38%. The difference among the three groups was statistically significant (F=18.47, p<0.001). A similar pattern was observed for hip-fracture probability, which declined from 9.63±5.29% in the deficient group to 6.91±4.18% in the insufficient group and 4.37±3.12% in the sufficient group (F=17.42, p<0.001). Thus, poorer vitamin D status was associated with a significantly greater estimated probability of both major osteoporotic and hip fractures. Table 4B: Fracture probability according to BMD classification BMD classification n Major osteoporotic-fracture probability, Mean (SD), % 95% CI Hip-fracture probability, Mean (SD), % 95% CI Normal BMD 39 9.72 (4.61) 8.23–11.21 3.84 (2.31) 3.09–4.59 Osteopenia 94 16.38 (6.83) 14.98–17.78 7.21 (4.17) 6.36–8.06 Osteoporosis 67 24.91 (9.14) 22.68–27.14 13.76 (6.82) 12.10–15.42 Test of significance ANOVA F=56.54 ANOVA F=57.31 P value <0.001* <0.001* Table 4B shows that estimated fracture risk increased markedly with worsening BMD classification. The mean 10-year probability of a major osteoporotic fracture was 9.72±4.61% among patients with normal BMD, 16.38±6.83% among those with osteopenia and 24.91±9.14% among those with osteoporosis. This increasing trend was statistically significant (F=56.54, p<0.001). Similarly, the mean hip-fracture probability increased from 3.84±2.31% in the normal-BMD group to 7.21±4.17% in the osteopenic group and 13.76±6.82% in the osteoporotic group (F=57.31, p<0.001). Patients with osteoporosis consequently had approximately 2.6 times the major osteoporotic-fracture probability and 3.6 times the hip-fracture probability observed among patients with normal BMD. Table 4C: Correlation with estimated fracture probability Explanatory variable Major osteoporotic-fracture probability, r (95% CI) Test; P value Hip-fracture probability, r (95% CI) Test; P value Serum 25(OH)D -0.36 (-0.48 to -0.23) t=-5.43; <0.001* -0.39 (-0.50 to -0.27) t=-5.96; <0.001* Lumbar-spine T-score -0.51 (-0.61 to -0.40) t=-8.34; <0.001* -0.54 (-0.63 to -0.43) t=-9.03; <0.001* Femoral-neck T-score -0.57 (-0.66 to -0.47) t=-9.76; <0.001* -0.62 (-0.70 to -0.53) t=-11.12; <0.001* Major and hip-fracture probabilities 0.71 (0.63–0.77) t=14.19; <0.001* - - *Statistically significant at p<0.05. Table 4C presents the correlations of vitamin D and site-specific BMD with estimated fracture probability. Serum 25(OH)D demonstrated significant inverse correlations with major osteoporotic-fracture probability (r=-0.36; 95% CI: -0.48 to -0.23; p<0.001) and hip-fracture probability (r=-0.39; 95% CI: -0.50 to -0.27; p<0.001). Lumbar-spine T-score also showed significant inverse correlations with major osteoporotic-fracture probability (r=-0.51; p<0.001) and hip-fracture probability (r=-0.54; p<0.001). Femoral-neck T-score had stronger inverse correlations with major osteoporotic-fracture probability (r=-0.57; 95% CI: -0.66 to -0.47; p<0.001) and hip-fracture probability (r=-0.62; 95% CI: -0.70 to -0.53; p<0.001). This indicated that decreasing femoral-neck T-score was strongly associated with increasing estimated fracture probability, particularly for hip fracture. Major osteoporotic and hip-fracture probabilities were themselves strongly and positively correlated (r=0.71; 95% CI: 0.63–0.77; p<0.001). Table 5. Univariable linear regression of serum vitamin D as a predictor of lowest BMD T-score (N=200) Predictor Unstandardized β SE Standardized β 95% CI for β t value P value Serum 25(OH)D, per 1 ng/mL increase 0.044 0.0068 0.420 0.031-0.058 6.51 <0.001* Constant -3.190 0.141 -3.468 to -2.912 -22.62 <0.001* Model summary: R²=0.176; adjusted R²=0.172; F(1,198)=42.38; p<0.001. Univariable linear regression demonstrated that serum 25(OH)D was a significant positive predictor of the lowest BMD T-score. Each 1 ng/mL increase in serum 25(OH)D was associated with a 0.044-unit increase in the BMD T-score (β=0.044; 95% CI: 0.031–0.058; p<0.001). The model was statistically significant (F=42.38; p<0.001) and serum vitamin D alone explained 17.6% of the variation in BMD (R²=0.176).

The present study evaluated the interrelationship between serum vitamin D status, BMD and estimated fracture probability among 200 patients presenting with low-energy fractures. The principal findings were a low mean serum 25(OH)D concentration of 18.74±8.63 ng/mL, vitamin D deficiency in 55.5%, vitamin D below 30 ng/mL in 84.5%, and low BMD in 80.5% of patients. Vitamin D was positively correlated with BMD and inversely correlated with estimated fracture probability. BMD, particularly at the femoral neck, demonstrated a stronger association with estimated fracture probability than serum vitamin D. Vitamin D status among patients with low-energy fractures The mean serum 25(OH)D concentration in the present study was significantly below the prespecified sufficiency threshold of 30 ng/mL. Fu et al. (2015)[1], in a matched case-control study of 349 postmenopausal women with a hip fracture and 349 controls, reported vitamin D deficiency in 71.3% of fracture patients compared with 63.6% of controls. Their findings support the high frequency of vitamin D deficiency observed in the present study, although the reported prevalence was higher than the present value of 55.5%. Differences in age, ethnicity, season of sampling, dietary intake, sunlight exposure, assay method and the threshold used to define deficiency may account for this variation. Niikura et al. (2019)[5] examined 360 elderly Japanese patients with fragility hip fractures and reported vitamin D insufficiency in 71.7% and deficiency in 21.4%, demonstrating that inadequate vitamin D status was present in more than 90% of their population. Similarly, Han et al. (2020)[6] evaluated 732 patients with low-energy hip fractures and found vitamin D deficiency in 83.3%, insufficiency in 11.9%, and normal vitamin D levels in only 4.8%. These findings are comparable with the present study, in which only 15.5% had serum 25(OH)D of at least 30 ng/mL. Dadra et al. (2019)[7] also reported a high prevalence of vitamin D deficiency, secondary hyperparathyroidism and osteoporosis among Indian patients presenting with proximal-femur fragility fractures. The similarity is particularly relevant because geographical location, skin pigmentation, clothing patterns, dietary habits and limited effective sunlight exposure may produce a substantial burden of hypovitaminosis D even in regions with abundant sunlight. The present findings therefore reinforce the need to evaluate vitamin D status after a low-energy fracture rather than assuming adequacy based on climate alone. Vitamin D status according to fracture site Patients with hip or proximal-femur fractures had the lowest mean serum 25(OH)D concentration at 15.62±7.44 ng/mL, compared with 20.41±8.71 ng/mL in distal-radius fractures and 19.37±8.26 ng/mL in vertebral, proximal-humerus or other fractures. The difference was statistically significant. The particularly low level among patients with hip fractures may reflect greater age, frailty, reduced outdoor activity, poorer nutrition and a higher frequency of institutionalisation or dependence. Yu et al. (2021)[9], in a study of 268 patients with fragility hip fractures, identified vitamin D deficiency in 200 patients (74.6%) and reported that lower vitamin D was associated with older age and poorer BMD. This supports the present observation that hip-fracture patients represented the group with the lowest vitamin D concentration. The greater degree of deficiency reported by Yu et al. may be attributable to the exclusive inclusion of hip fractures, whereas the present study included distal-radius, vertebral and proximal-humerus fractures as well. Biochemical findings Although mean uncorrected serum calcium was within the reference range, corrected calcium and phosphorus were slightly reduced, while alkaline phosphatase was significantly elevated. This biochemical pattern is compatible with altered calcium-phosphate homeostasis and increased bone turnover in at least a proportion of the participants. A normal serum calcium value does not exclude vitamin D deficiency because compensatory parathyroid hormone secretion may preserve circulating calcium at the expense of skeletal mineral stores. Wang et al. (2020)[8] reported that elderly hip-fracture patients with osteoporosis had lower serum calcium and significantly lower serum 25(OH)D than those without osteoporosis. Mean vitamin D was 25.43±6.35 ng/mL in osteoporotic patients compared with 30.70±7.17 ng/mL among non-osteoporotic patients (p<0.01). Vitamin D insufficiency and deficiency were also more frequent in the osteoporosis group. These findings provide biological support for the combined abnormalities of vitamin D, corrected calcium and BMD observed in the present study. Bone mineral density findings The femoral neck was the most severely affected DXA site, with a mean BMD of 0.67±0.12 g/cm² and a mean T-score of -2.48±1.11. The corresponding lumbar-spine and total-hip T-scores were -2.31±1.04 and -2.12±0.94, respectively. Based on the lowest valid T-score, 47.0% of patients had osteopenia, 33.5% had osteoporosis and only 19.5% had normal BMD. Thus, four out of every five patients with a low-energy fracture had low BMD. Wang et al. (2020)[8] found osteoporosis in 40% of elderly patients with hip fractures, which was moderately higher than the 33.5% prevalence in the present mixed-fracture population. Yu et al. (2021)[9] similarly demonstrated extensive reductions in femoral-neck and hip BMD among patients with fragility hip fractures. These studies support the present finding that femoral-neck BMD is particularly compromised in patients experiencing low-energy fractures. Nevertheless, the occurrence of fractures among 19.5% of participants with normal BMD demonstrates that skeletal fragility is not explained by BMD alone. Bone microarchitecture, falls, age, previous fractures, glucocorticoid exposure, neuromuscular impairment and other clinical risk factors contribute independently to fracture risk. LeBoff et al. (2022)[11] emphasised that a fragility fracture may establish a diagnosis of osteoporosis or a high-risk clinical state even when the measured T-score is above -2.5, particularly in patients with hip or vertebral fractures. This supports the combined use of DXA and clinical risk assessment rather than reliance on the T-score alone. Relationship between vitamin D and BMD Serum 25(OH)D was moderately and positively correlated with the lowest BMD T-score (r=0.42, 95% CI: 0.30–0.53; p<0.001). Therefore, patients with higher vitamin D concentrations tended to have less severely reduced BMD. Swanson et al. (2015)[2], in the Osteoporotic Fractures in Men study, similarly found that higher serum 25(OH)D was associated with higher baseline BMD, slower hip BMD loss and lower hip-fracture risk. Their longitudinal observations strengthen the biological plausibility of the present cross-sectional association. Wang et al. (2018)[4] also reported that individuals with adequate vitamin D had higher femoral-neck and total-hip BMD and a lower 10-year probability of major osteoporotic fracture than participants with inadequate vitamin D. Their findings are closely aligned with the present results, in which vitamin D-deficient patients had higher estimated probabilities of both major osteoporotic and hip fractures. The positive relationship between vitamin D and BMD may be explained by the role of vitamin D in intestinal calcium and phosphate absorption and skeletal mineralisation. Chronic vitamin D deficiency may increase parathyroid hormone secretion, bone turnover and cortical bone loss. However, age, frailty, nutritional status, physical activity and comorbidities may influence both vitamin D and BMD. Consequently, the observed correlation does not by itself establish that vitamin D deficiency caused the reduction in BMD. Vitamin D and estimated fracture probability Vitamin D-deficient patients had mean major osteoporotic and hip-fracture probabilities of 20.84% and 9.63%, respectively, compared with 12.43% and 4.37% among vitamin D-sufficient patients. Serum vitamin D was inversely correlated with major osteoporotic-fracture probability (r=-0.36) and hip-fracture probability (r=-0.39). Feng et al. (2017)[3], in a meta-analysis of 19 prospective cohort or nested case-control studies, found that low serum 25(OH)D was associated with increased risks of total fracture (RR=1.25, 95% CI: 1.06–1.43) and hip fracture (RR=1.48, 95% CI: 1.29–1.68). Each standard-deviation reduction in serum vitamin D was associated with a 40% increase in hip-fracture risk. These findings are consistent with the inverse relationships observed in the present study. The weaker correlations observed for vitamin D compared with BMD were expected because serum vitamin D is not directly included as a variable in conventional FRAX. Its relationship with FRAX probability may be mediated by age, BMD, falls, frailty and secondary osteoporosis. Furthermore, a single serum 25(OH)D measurement reflects recent vitamin D status and may not accurately represent lifetime exposure. BMD and estimated fracture probability The mean major osteoporotic-fracture probability increased from 9.72% in patients with normal BMD to 16.38% in osteopenia and 24.91% in osteoporosis. Similarly, hip-fracture probability increased from 3.84% to 7.21% and 13.76%, respectively. The lowest BMD T-score demonstrated significant inverse correlations with major osteoporotic-fracture probability (r=-0.57) and hip-fracture probability (r=-0.62). Femoral-neck T-score had the strongest association with hip-fracture probability (r=-0.62), which was anticipated because femoral-neck BMD is the DXA measurement incorporated into FRAX. Kanis et al. (2020)[10] explained that FRAX combines femoral-neck BMD with age, sex and clinical risk factors to estimate individualised 10-year probabilities of hip and major osteoporotic fractures. The strong relationship between femoral-neck BMD and FRAX in the present study therefore supports the internal clinical consistency of the findings. Although fracture probabilities were highest in osteoporosis, patients with osteopenia also had clinically important mean probabilities. This supports probability-based risk stratification because a substantial number of fractures occur in individuals who do not meet the DXA threshold for osteoporosis. The strong positive correlation between major osteoporotic and hip-fracture probabilities (r=0.71) further indicates that common factors such as age, prior fracture and low femoral-neck BMD contribute to both outcomes. Clinical implications and comparison with intervention evidence The present observational results support screening for vitamin D deficiency, BMD reduction and subsequent fracture risk following a low-energy fracture. However, an association between low vitamin D and fracture risk should not be interpreted as proof that vitamin D supplementation alone will prevent fractures. Bolland et al. (2018)[12], in a systematic review and trial-sequential meta-analysis, concluded that vitamin D supplementation alone did not prevent fractures or falls and did not produce clinically meaningful improvement in BMD. Yao et al. (2019)[13] similarly found no significant fracture reduction with vitamin D alone. In contrast, their meta-analysis of six trials involving 49,282 participants showed that combined daily vitamin D and calcium supplementation reduced any fracture by 6% (RR=0.94, 95% CI: 0.89–0.99) and hip fracture by 16% (RR=0.84, 95% CI: 0.72–0.97). Accordingly, patients with documented deficiency should receive appropriate correction, but secondary fracture prevention should also include adequate calcium intake, osteoporosis pharmacotherapy when indicated, fall-risk reduction, exercise and management through a fracture liaison service. Univariable linear regression The significant positive relationship between serum vitamin D and BMD observed in the present study agrees with the findings of Swanson et al. (2015), who reported that higher serum 25(OH)D concentrations were associated with higher baseline hip BMD and slower subsequent loss of hip BMD among older women. Their findings support the biological and clinical relationship between adequate vitamin D status and preservation of skeletal mineral density. Similarly, Feng et al. (2017), in a meta-analysis examining serum 25(OH)D and fracture outcomes, observed that lower vitamin D concentrations were associated with greater risks of total and hip fractures. Although their principal outcomes were fractures rather than BMD, the findings are consistent with the present regression result because reduced BMD represents an important pathway through which inadequate vitamin D may contribute to skeletal fragility. Wang et al. (2020) found that elderly patients with hip fractures and osteoporosis had significantly lower serum 25(OH)D concentrations than those without osteoporosis. Vitamin D deficiency was also more frequent among patients with osteoporosis. These observations correspond with the present finding that increasing vitamin D concentration was associated with a progressively higher, or better, BMD T-score. Yu et al. (2021) likewise demonstrated a positive association between serum 25(OH)D concentration and BMD among patients with hip fractures, particularly at the femoral neck and total hip. This supports the direction of association observed in the present study. Nevertheless, vitamin D explained only 17.6% of BMD variability in the current analysis, suggesting that age, sex, menopausal status, BMI, calcium intake, physical activity, glucocorticoid exposure and comorbidities also contribute substantially to bone density. As the present model was univariable, the relationship should be interpreted as an unadjusted association rather than evidence that vitamin D independently determines BMD.

The study demonstrated a high prevalence of vitamin D inadequacy and reduced BMD among patients presenting with low-energy fractures. More than half of the participants had vitamin D deficiency, while approximately four-fifths had either osteopenia or osteoporosis. Serum 25(OH)D showed a significant positive relationship with BMD and significant inverse relationships with the estimated probabilities of major osteoporotic and hip fractures. Fracture probability increased progressively from patients with sufficient vitamin D to those with vitamin D deficiency and from normal BMD to osteopenia and osteoporosis. Femoral-neck BMD demonstrated the strongest relationship with estimated hip-fracture probability. These findings suggest that low-energy fractures should be considered important indicators of compromised skeletal health. Patients presenting with such fractures should undergo comprehensive evaluation of vitamin D status, BMD and clinical fracture risk. Early correction of vitamin D deficiency, appropriate osteoporosis treatment, adequate calcium intake, fall-prevention measures and structured secondary-fracture prevention may help reduce the likelihood of subsequent fractures. However, the observed relationships were associative and did not establish that vitamin D deficiency independently caused low BMD or fractures. LIMITATIONS OF THE STUDY 1. The study was conducted at a single tertiary-care centre; therefore, its findings may not be generalisable to the wider community or to populations with different demographic, nutritional and environmental characteristics. 2. The cross-sectional design established associations but could not determine temporal or causal relationships between vitamin D deficiency, reduced BMD and fracture risk. 3. The study included only patients who had already sustained a low-energy fracture and did not include an age- and sex-matched control group without fractures. 4. Serum 25(OH)D was measured only once. Seasonal variation, recent sunlight exposure, dietary intake and preceding supplementation could have influenced the measured concentration. 5. Differences in vitamin D assay methods and the use of prespecified cut-offs for deficiency, insufficiency and sufficiency may limit comparisons with studies using other laboratory techniques or thresholds. 6. BMD was measured using DXA, which evaluates bone quantity but does not fully assess bone microarchitecture, geometry, material strength or other components of bone quality. 7. Degenerative changes, vertebral deformity, vascular calcification or positioning errors may have influenced lumbar-spine BMD measurements. 8. FRAX estimates were influenced by age and femoral-neck BMD and did not directly incorporate vitamin D concentration, falls, fracture recency, fracture number, lumbar-spine BMD or dose-response relationships for glucocorticoids and smoking. 9. FRAX was used among patients who had already sustained a low-energy fracture; therefore, it represented the estimated probability of a subsequent fracture rather than the probability of the index fracture. 10. Differences in age, sex, menopausal status, fracture site, comorbidities, physical activity, nutritional status and medication exposure could have confounded the observed association because multivariable adjustment was not performed. 11. Certain relevant biochemical measurements, such as parathyroid hormone, magnesium and bone-turnover markers, were not evaluated in all participants. 12. The study did not include prospective follow-up to determine incident refractures, changes in BMD, treatment response, functional recovery or mortality.

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