Inappropriate supplementation of Vitamin D can result in toxicity: a crosssectional study of paediatrics population.

OBJECTIVE: To evaluate children with suspected or definite hypervitaminosis D with respect to prevalence, clinical manifestations and pharmacological aspects. METHODS: The retrospective cross-sectional study was conducted at the Aga Khan University Hospital, Karachi, and comprised medical records from January 1 to December 31, 2018, of children aged <18 years with 25-hydroxyvitamin D levels >50ng/ml. Clinical and pharmacological data was retrieved. Data was analysed using SPSS 23. RESULTS: Of the 118,149 subjects visiting the clinical laboratory during the study period, children tested for serum 25-hydroxyvitamin D levels were 16,316(13.8%) who had a median age of 9.78 years (interquartile range: 10.2 years). Children who registered for consultation were 2720(16.6%), and, out of them, 602(22%) had serum 25-hydroxyvitamin D >50ng/ml. The median 25-hydroxyvitamin D levels and age were 70.1ng/ml (interquartile range: 100ng/ml) and 3.1 years (interquartile range: 17.93 years), respectively, and 345(57.3%) of them were boys. Children supplemented with vitamin D were 197(33.1%) and 193(97.9%) of them were prescribed by physicians. Mega-doses were taken by 68(34.17%), while the remaining had used various combinations in syrup or tablet forms. Commonly prescribed mega-doses were 600,000IU 30((44.1%) and 200,000IU 31(45.5%) injections of vitamin D. The primary indications were pains/aches in 51(25.8%) cases, developmental delay 50(25.3%), and vitamin D deficiency 49(24.8%). The main symptoms of hypervitaminosis D or toxicity were abdominal pain 27(13.7%) and constipation 31(15.7%). CONCLUSIONS: Children should be given vitamin D supplements with caution as prolonged supplementation and repeated mega-doses can result in toxicity which may cause serious consequences.

Practices of vitamin D supplementation leading to vitamin D toxicity: Experience from a Low-Middle Income Country.

INTRODUCTION: The trend of prescribing VD preparations for nonspecific body aches and self-medication has increased significantly. The importance of vitamin D toxicity (VDT) has been underestimated and under recognized. This study was done to determine the frequency toxicity (>150 ng/ml) in subjects for 25-hydroxyvitamin D (25OHD) and evaluate the vitamin D (VD) supplements used by these subjects. METHODOLOGY: This descriptive cross-sectional study was conducted at the Section of Chemical Pathology, Aga Khan University Hospital Karachi from April 2020 to March 2021. Subjects with 25OHD toxicity were contacted and information related to history of calcium and VD supplementation were collected. The statistical analysis was performed using the Microsoft Excel 2016. RESULTS: Over a year period 105398 subjects were tested for serum 25OHD, of which 0.34% (n = 364) subjects had 25OHD level of >150 ng/ml. After satisfying exclusion criteria 186 subjects (78 were <18 years of age and 108 were adults) were included in final analysis. All of these were using VD supplements and the main indications were delayed growth/short height (43.7%, n = 34) and aches or pains in (54.6%, n = 59) in pediatric and adult subjects respectively.Most of the subjects were taking supplements orally (74.1%, n = 138). Commonly prescribed preparation in adults and pediatric was 200,000 IU (70.4%, n = 76) and 400 IU (35.9%, n = 28) respectively. Most subjects took supplements for 1-3 months (68.3%, n = 127). Stated total supplementation ranged from 20,000 IU to 3600,000 IU in pediatric subjects and 200,000 IU to 96,00,000 IU in adults. CONCLUSIONS: Supplementation is a leading cause of potential toxic levels of 25OHD. The condition can be prevented by careful use of VD supplements and consistent monitoring.

Bridging the gaps in secondary fracture prevention at a single center in Pakistan-compliance with the IOF best practice framework.

PURPOSE: The International Osteoporosis Foundation (IOF) formulated a set of best practice framework as an international benchmark for secondary fracture prevention (SFP) and fracture liaison services (FLS), delineating essential elements of service delivery. The aim of this audit was to assess compliance with the IOF standards for patients ≥ 50 years presenting with fragility hip fractures at a tertiary care center in Pakistan. METHODS: A retrospective sample of hip fracture cases from Jan 2019 to Dec 2019, treated at the section of Orthopedic Surgery, Aga Khan University, Karachi, was conducted. After excluding high energy trauma cases and patients younger than 50 years of age, medical records were audited, using a pre-structured Performa based on IOF standards. Compliance level of 0, 1, 2, and 3 was recorded as defined by IOF. Microsoft excel was used for data analysis. RESULTS: A compliance level of 3 was recorded for patient identification and fall prevention services, whereas level 1 was attained for database maintenance for 25 (100%) cases. For medication initiation, level 0 was recorded for all the cases; however, 8 (32%) cases were prescribed calcium and vitamin D supplements. For the standards, including post-fracture assessment timing, evaluation of secondary causes of osteoporosis, multifaceted assessment, medication review, communication strategy, and long-term management, a level 0 was noted for 25 (100%) cases. Moreover, no recommended assessment guidelines were followed uniformly. CONCLUSION: The care gaps identified require substantial efforts to ensure adequate implementation of the overall best practice standards for SFP, necessitating the need for FLS initiation and establishment of fracture care pathway.

Clinical characteristics and outcomes of patients presenting with hip fractures at a tertiary care hospital in Pakistan.

Osteoporosis remains under-recognized and sub-optimally managed in Pakistan, with a lack of awareness that minimal impact hip fracture is a manifestation of low bone mineral density (BMD). PURPOSE: Hip fracture is often the first clinical presentation of osteoporosis and an opportunity to intervene and reduce future fracture risk. Our aim was to understand the current practices in Pakistan related to bone health in patients presenting with a hip fracture. METHODS: This is a retrospective study at a tertiary care center in Pakistan of patients admitted with a hip fracture. Data collected includes previous fracture history, known preceding diagnosis of low BMD medication details, comorbidities, and DXA results. RESULTS: Two hundred ten patients were studied. The mean age of patients was 73.1 years, with 112 (53.3%) women. Most (195 (92.9%)) had presented with a low-impact hip fracture, with 17 (8.1%) reporting previous history of fracture. None had been treated with osteoporosis medications prior to fracture. Nineteen (9%) were on calcium and vitamin D supplements prior to fracture; of the minority who were screened, all were vitamin D deficient and subsequently discharged on vitamin D supplements. No one was prescribed medications to reduce fracture risk at discharge. CONCLUSION: This study reveals that patients admitted with minimal impact hip fractures in Pakistan are rarely evaluated for low BMD and not started on osteoporosis medications even after presenting with a typical osteoporosis-related fracture. This underscores the need for health provider education about osteoporosis as a major cause for hip fractures and the need to intervene for future fracture risk reduction.

High Burden of Subclinical Lead Toxicity after Phase Out of Lead from Petroleum in Pakistan.

OBJECTIVE: To evaluate the frequency of subclinical lead toxicity. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, from January 2011 to December 2014. METHODOLOGY: Analysis of laboratory data for blood lead levels (BLL) was performed. Lead was tested by atomic absorption spectrometer. For all subjects, only initial test results were included while the results of repeated testing were excluded. Exemption was sought from institutional ethical review committee. BLL of 2-10 ug/dl and 10-70 ug/dl in children and adults, respectively were taken as subclinical lead toxicity. RESULTS: Amongst the total number of subjects tested (n=524), 26.5% (n=139) were children (<16 years) while rest were adults. Overall median BLLs was 6.4 ug/dl (20.9-3.1). The median BLL was 4 ug/dl (6.7-2.6) in children and 8.3 ug/dl (27.9-3.4) in adults, respectively. The BLL increased with age; higher levels were observed in age range 21-30 years of subjects [median lead level 16.9 ug/dl (36.1-4)] and lower level [4.2 ug/dl (6.8-2.6)] in children with <10 years of age. Only 16% (n=22) children had desirable lead levels while most had either subclinical (76%, n=106) or toxic lead levels (8%, n=11). In adults, (55%, n=212) subjects had desired lead levels, and 40% (n=154) and 4.99% (n=19) had subclinical and toxic lead levels. CONCLUSION: Presence of subclinical lead poisoning even after phasing out of lead petroleum in Pakistanis is alarming, especially in children. A national population-based study to determine the lead status and targeted intervention to identify potential sources is need of the time.

Response of a single 'mega intramuscular dose' of vitamin D on serum 25OHD and parathyroid hormone levels.

OBJECTIVE: To determine the changes produced in serum 25OHD and iPTH levels after 600,000 IU of injection cholecalciferol in volunteers. STUDY DESIGN: Interventional study. PLACE AND DURATION OF STUDY: Section of Chemical Pathology, Department of Pathology and Microbiology, the Aga Khan University Hospital, Karachi, from June 2009 - June 2010. METHODOLOGY: Volunteers of either gender aged 18-40 years with known 25OHD, calcium (Ca), creatinine (Cr) and phosphorous (P) levels were included in the study. Subjects on therapy like vitamin D and calcium supplements, corticosteroids or anti-epileptic medicines, primary hyperparathyroidism and hypercalcaemia, with co-morbidity like renal failure, liver disease and history of malabsorption, diarrhea or hyperthyroidism were excluded. All volunteers were given an intramuscular injection of vitamin D3 (cholecalciferol, 600,000 IU). After 8 weeks, serum 25OHD, iPTH, Ca and P levels were determined again. For 25OHD level, cut-off of ² 50 nmol/l was defined as deficient, 50-75 nmol/l as insufficient and ³ 75 as optimal level. RESULTS: Mean 25OHD and iPTH levels were 35.06 ± 16.6 nmol/l and 81.15 ± 76.78 pg/ml respectively at baseline. Seventeen volunteers were 25OHD deficient. Five had high iPTH levels (25%) (mean 156 ± 123.7 pg/ml). 25OHD and iPTH showed a significant inverse correlation at baseline (< 0.01). After 8 weeks of injection vitamin D 25OHD levels became optimal in 6 subjects (35%) [mean 92.9 ± 16.6 nmol/l]. It remained low in 5 volunteers (25%) [mean 41.6 ± 9.6 nmol/l] while insufficient levels were seen in 9 volunteers (40%) [mean 63.3±5.8 nmol/l]. Follow-up mean Ca, P and iPTH were 2.25 mmol/l (± 0.09), 1.1 (± 0.1) and 47.52 pg/ml (± 22.56) respectively. A significant increase in mean 25OHD level was seen at follow-up (p < 0.01), while the change in PTH was insignificant (p=0.05). CONCLUSION: Single mega-dose of cholecalciferol achieved optimal levels of 25OHD in 35% of subjects after eight weeks of supplementation.