Vitamin D level among patients with unexplained musculoskeletal symptoms

Background: Unexplained musculoskeletal (MSK) symptoms some�mes pose diagnos�c and management challenges and can lead to prolonged suﬀering and disability. Hypovitaminosis D could be a reason for such symptoms. This study aimed to determine the vitamin D level among pa�ents with unexplained MSK symptoms. Methods: A cross-seconal study was conducted in a private clinic of Cha�ogram city, Bangladesh. A total of 110 unexplained MSK pa�ents were enrolled conveniently. MSK symptoms were assessed by rheumatologist and serum vitamin D levels were measured according to the standard laboratory procedure. Descrip�ve and logis�c regression analyses were done. Principal component analysis was performed for the reduc�on of MSK symptoms. Results: The median (interquar�le range) vitamin D level was 24.6 (20.0–29.0) ng/mL. Hypovitaminosis D (<30 ng/mL) was observed in 80.0% (95% CI: 71.3%–87.0%) respondents. Pa�ents who had diﬃculty in climbing stairs, bone pain and muscle cramp had 79.8%, 84.9% and 79.8% hypovitaminosis D respec�vely. In logis�c regression analysis, overweight deﬁned by body mass index ≥25 kg/m 2 (OR 5.5, 95% CI 1.7–


INTRODUCTION
Musculoskeletal (MSK) symptoms encompass a wide range of clinical presentations, including pain, stiffness, and weakness affecting the muscles, bones, and joints. 1 These symptoms pose diagnostic challenges due to their diverse etiologies, often leading to prolonged suffering and disability for patients. 2Occasionally some MSK symptoms cannot be explained by any specific MSK disease and refers as non-specific or unexplained MSK symptoms.The complexity of unexplained MSK symptoms necessitates further exploration of potential contributing factors, including nutritional deficiencies, such as low levels of vitamin D. 3 Vitamin D, a secosteroid hormone synthesized in the skin upon sunlight exposure and obtained through dietary sources, plays a pivotal role in maintaining skeletal health and various physiological processes. 4It exerts pleiotropic effects on bone metabolism, immune modulation, muscle function, and overall well-being.

Deficiency or insufficiency of vitamin D has been implicated
in the pathogenesis of several musculoskeletal disorders, including osteoporosis, osteomalacia, and muscle weakness. 5Consequently, assessing the vitamin D status among patients with unexplained MSK symptoms may offer valuable insights into the underlying mechanisms of these symptoms. 6,7 ally, adults with vitamin D deficiency typically exhibit various MSK symptoms, including bone pain, muscle weakness, muscle spasm, muscle cramp. 8The MSK manifestations of vitamin D deficiency may include joint discomfort, fatigue, walking difficulties with or without stair climbing, and difficulty rising from a squatting position.

ORIGINAL ARTICLE
In Asia, vitamin D deficiency is more prevalent.

Study design and population
This were excluded during analysis.Informed written consent was obtained from all participants before their enrollment into the study.

Data collection
Data collection was performed using a semi-structured questionnaire designed specifically for this study.Blood samples were collected from cubital vein by using regular red-top Vacutainers.Vitamin D analysis was done from fresh serum.Beckman Coulter Access-2 Analyzer was used to measure 25-hydroxy vitamin D total (vitamin D2 and D3) by using the Chemiluminescent Immunoassay method.
Hypovitaminosis D was defined as a serum vitamin D level below 30 ng/mL. 11

Ethical issues
The authors are accountable for all aspects of the work

Statistical analysis
Data

Key Findings
We aimed to investigate the vitamin D levels among

Comparison with similar researches
The high prevalence of hypovitaminosis D observed in our study is in line with studies conducted in Iran (95.4%) and Hongkong (84.1%) as most of the patients had vitamin D deficiency. 12,13 s we observed that overweight (BMI ≥25 kg/m 2 ) was a significant predictor of hypovitaminosis D among patients with unexplained MSK symptoms however, previous studies that also demonstrated a relationship between higher body mass index and lower vitamin D levels. 14Adipose tissue can sequester vitamin D, leading to reduced circulating levels in individuals with excess body fat. 15Therefore, the observed association between overweight status and hypovitaminosis D highlights the importance of considering body composition as a potential risk factor in patients with unexplained MSK symptoms.

Explanations of findings
The high prevalence of hypovitaminosis D among patients with unexplained MSK symptoms observed in our study warrants further explanation.Vitamin D deficiency is often asymptomatic, but it can manifest as muscle cramps and bone pain. 16In line with these findings, we observed that the highest percentage of patients experiencing muscle cramps had low vitamin D levels.Other studies have also reported an association between vitamin D deficiency and proximal myopathy, with more pronounced effects observed at vitamin D levels below 10 ng/mL. 17Muscle weakness and pain, which can be attributed to vitamin D deficiency, have been documented in both adults and children. 18fficulty in climbing stairs is a symptom commonly associated with proximal muscle weakness.Interestingly, in our study, we did not find any patients with rheumatic or neurological diseases who had difficulty climbing stairs.This may be explained by the presence of vitamin D deficiency or insufficiency, which can contribute to muscle weakness and compromise physical function. 19e underlying mechanisms of bone-associated pain in humans and animals are not fully understood.Bone disorders such as osteoporosis, characterized by decreased bone density and increased fragility, can lead to bone-associated pain.Animal models are being utilized to investigate the mechanisms of pain and develop improved treatments. 20Serum 25-hydroxy vitamin D deficiency has a possible contributory role for the development of pain and tenderness over the tibial bone. 21The intensity of bone pain is directly related to vitamin D deficiency. 22In our study, approximately two -thirds of the patients reported experiencing bone pain, and 85% of them had low vitamin D levels.
The correlation between bone pain intensity and vitamin D deficiency further supports the role of vitamin D in bone health.Adequate vitamin D levels are crucial for maintaining bone health and reducing the risk of skeletal complications. 23The observation that a substantial proportion of patients with bone pain in our in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013) and we assured that the data would be used for scientific research only.This study was approved by the Institutional Review Board of the Chattogram Maa-O-Shishu Hospital Medical College.Written informed consent was taken from all the patients before taking part of the study.
patients with unexplained musculoskeletal (MSK) symptoms.The results revealed that, the prevalence of hypovitaminosis D among the study participants was remarkably high (80%).This study identified overweight (BMI ≥25 kg/m 2 ) as a significant predictor of hypovitaminosis D. PCA revealed three out of seven MSK symptoms such as difficulties in climbing stairs, bone pain, and muscle cramp scored highest in each component.Strengths and limitationsThis study has several strengths, including the comprehensive assessment of musculoskeletal symptoms among patients with unexplained MSK symptoms.The study utilized standardized laboratory methods to measure serum vitamin D levels, ensuring the reliability of the results.Additionally, the study considered various potential confounding factors, ruling out conditions such as active arthritis, myopathy, connective tissue diseases, trauma, and disabilities through comprehensive clinical, radiological, and laboratory examinations by the researcher.However, several limitations should be acknowledged.First, we could not come up with the estimated sample size and the samples were selected conveniently and from a city based private clinic.Therefore, the study has a limitation of adequate power of the statistical tests and generalizability.Second, the cross-sectional design of the study limits causal inferences.Longitudinal studies are necessary to establish temporal relationships between vitamin D levels and musculoskeletal symptoms.
study had low vitamin D levels strengthens the evidence for the association between vitamin D deficiency and bone-related symptoms.Obesity demonstrated as a risk factor for hypovitaminosis D among patients with unexplained MSK symptoms.This finding aligns with the common observation of hypovitaminosis D among obese individuals.One possible explanation is the volumetric dilution of vitamin D concentration into the larger volumes of fat, serum, liver, and muscle in obese subjects.This phenomenon can contribute to lower levels of bioavailable vitamin D and subsequently lead to hypovitaminosis D in individuals with obesity. 24Implications and actions needed Taken together, the findings of our study have important implications for clinical practice and public health.Given the high prevalence of hypovitaminosis D among patients with unexplained MSK symptoms, it is crucial to include vitamin D assessment as part of the diagnostic workup for individuals presenting with musculoskeletal symptoms.Further research is needed to elucidate the precise mechanisms underlying these associations and to explore the potential benefits of vitamin D supplementation in managing musculoskeletal symptoms in this patient population.The association between overweight status and hypovitaminosis D highlights the need to consider body composition, particularly obesity, as a potential risk factor for vitamin D deficiency among patients with unexplained MSK symptoms.Conclusion Hypovitaminosis D was quite common in patients with unexplained MSK symptoms and overweight associated with it.Therefore, highlighting the importance of considering Hypovitaminosis D and body composition while treating unexplained MSK symptoms.Further studies in representative samples are necessary.

Vitamin D level among patients with unexplained musculoskeletal symptoms
ABSTRACTBackground: Unexplained musculoskeletal (MSK) symptoms some mes pose diagnos c and management challenges and can lead to prolonged suffering and disability.Hypovitaminosis D could be a reason for such symptoms.This study aimed to determine the vitamin D level among pa ents with unexplained MSK symptoms.Methods: A cross-sec onal study was conducted in a private clinic of Cha ogram city, Bangladesh.A total of 110 unexplained MSK pa ents were enrolled conveniently.MSK symptoms were assessed by rheumatologist and serum vitamin D levels were measured according to the standard laboratory procedure.Descrip ve and logis c regression analyses were done.Principal component analysis was performed for the reduc on of MSK symptoms.Results: The median (interquar le range) vitamin D level was 24.6 (20.0-29.0)ng/mL.Hypovitaminosis D (<30 ng/mL) was observed in 80.0% (95% CI: 71.3%-87.0%)respondents.Pa ents who had difficulty in climbing stairs, bone pain and muscle cramp had 79.8%, 84.9% and 79.8% hypovitaminosis D respec vely.In logis c regression analysis, overweight defined by body mass index ≥25 kg/m 2 (OR 5.5, 95% CI 1.7-17.4)was significantly associated with hypovitaminosis D. Conclusions: Hypovitaminosis D was common in pa ents with unexplained MSK symptoms and overweight was significantly associated with it.Further studies in representa ve samples are necessary.

TABLE 1 Sociodemographic status and vitamin D level in patients with unexplained musculoskeletal symptoms
were analysed by using Statistical Product and Service Solutions for windows, version 26.Mean, standard deviation, median, interquartile range, Razzaque MA et al.Bangabandhu Sheikh Mujib Medical University Journal 2023; https://doi.org/10.3329/bsmmuj.v16i4.70186RESULTSOut of the 110 participants included in the study, 79 (71%) were women.The mean (standard deviation) age was 46.5 (12.8) years, with no significant differences observed between men and women.The majority of respondents (60.9%) fell within the age range of 18 to 49 years.Around 40% of the participants had an education level below higher secondary, and 90% were overweight (body mass index ≥25 kg/m 2 ) (TABLE1).Razzaque MA et al.Bangabandhu Sheikh Mujib Medical University Journal 2023; https://doi.org/10.3329/bsmmuj.v16i4.70186Vitamin D in musculoskeletal symptoms 207 a P value is normal versus hypovitaminosis D; all are chi-square test except bold is Fisher's exact test, age in years t test; b IQR: Interquartile range; c Mean (standard deviation) d Muscle weakness, fatigue, difficulties in squatting and pain in weight-bearing joints were not reported as the eigenvalues less than one in principal components analysis

TABLE 2 Univariate and multivariate analysis between vitamin D status and sociodemographic, musculoskeletal symptoms (n=110)
Model included age, sexes, education, body mass index, difficulty in climbing stairs, bone pain and muscle cramp simultaneously; b P<0.05 Razzaque MA et al.Bangabandhu Sheikh Mujib Medical University Journal 2023; https://doi.org/10.3329/bsmmuj.v16i4.70186Vitamin D in musculoskeletal symptoms 208 a