Clinical Drug Experience Knowledgebase

Maintenance of Vitamin D Sufficiency With Oral Vitamin D Supplementation in Malaysian Women of Malay and Indian Ethnicity With Post Menopausal Osteoporosis

This randomized controlled trial will evaluate the appropriate dose of Vitamin D required to maintain Vitamin D sufficiency amongst Indian and Malay PMO women. The study will last for six months. 150 PMO women of Indian and Malay ethnicity will be randomly allocated into 3 different dosing regimens i.e. (a) 25 000 IU/monthly (≈900 IU/day), (b) 50 000 IU/monthly (≈1800 IU/day) and (c) 50 000 IU/fortnightly (≈3300 IU/day). Each group will be containing an equal amount of Indian and Malay Individuals. Subjects will be recruited from the osteoporosis clinic at UMMC.

Inclusion Criteria

Post menopausal Osteoporosis women receiving treatment from the Osteoporosis Clinic, University of Malaya Medical Centre, Kuala Lumpur.
Resident in Malaysia, of South Indian descent or Muslim Malay wearing headscarf
Baseline serum 25(OH)D levels > 20 ng/ml or 50 nmol/L

Exclusion Criteria

Secondary osteoporosis e.g. glucocorticoid induced osteoporosis
Metabolic bone disease e.g. hypercalcaemia, primary hyperparathyroidism, hyperthyroidism, hypothyroidism, Paget's disease
Medications that interfere with bone / vitamin D metabolism e.g. hormone replacement therapy (HRT), Recombinant human parathyroid hormone i.e. Teriparatide, glucocorticoids, rifampicin and anticonvulsants
Calculated Creatinine Clearance of < 60 mls/min
Liver disease and Malabsorptive Diseases e.g. celiac disease, radiation, enteritis, active inflammatory bowel disease
Malignancy

All patients who fulfils the inclusion and exclusion criteria will be offered participation in the study and written consent will be obtained.

During the first visit blood samples will be taken and all relevant data will be obtained via an interview and questionnaire. Blood samples taken include total 25(OH)D, calcium, phosphate, albumin and PTH levels as well as full blood count, renal and liver function. Twenty-four hour urine calcium levels will also be measured.

A detailed past medical history and medication history focusing on use of bone-related therapies will be taken. Subjects will be requested to record medications that could affect vitamin D metabolism, e.g. glucocorticoids, Recombinant human parathyroid hormone i.e. Teriparatide, Hormone Replacement Therapy, Rifampicin and anticonvulsants. All calcium, vitamin D and multivitamin supplements taken within 3 months prior to the clinic visit will also be recorded.

Von Luschan scale will be used to determine the skin colour group that the patient belongs to. This scale contains 36 opaque glass tiles which is compared with the subject's skin on the back of the hands.

A validated sun exposure questionnaire evaluating amongst other things time spent outdoors with/without sun protection, body parts exposed to sun and travel in sunny areas; will be filled in with the help of a trained interviewer. Subsequently, the rule of nines will be used to calculate skin sun exposure. This number will be multiplied by the reported average sun exposure per week without sunscreen to calculate the sun exposure index. The subject's most recent dual x-ray absorptiometry results will be recorded.

All patients will receive advice on optimal sun exposure (10-20 minutes of sun exposure daily without sun block depending on gradations of skin colour) and dietary calcium requirements (1000 mg/day of elemental calcium) for treatment of osteoporosis.

A detailed diet history focusing on foods high in Vitamin D and calcium from a validated questionnaire will be obtained.

Subjects with 25(OH)D level of < 20ng/ml will initially receive a loading dose of 50 000 IU of Vitamin D3 weekly for 8 weeks as is standard clinical practice as recommended by the 2011 Endocrine Society guidelines, and serum 25(OH)D will be measured again after 8 weeks to ensure that levels are above 20ng/ml. They will then undergo an 8 weeks washout period in which the subjects will receive 25 000 IU of Vitamin D3 monthly for two months prior to randomization. If subjects are already > 20ng/ml at baseline they will proceed straight to randomisation.

All subjects will cease any previous over the counter Vitamin D supplements at study start. Thereafter subjects will be block randomized to either Vitamin D3 25 000 IU monthly, 50 000 IU monthly or 50 000 IU fortnightly of oral Cholecalciferol (Vitamin D3). Serum 25(OH)D, calcium, phosphate, iPTH and serum albumin will be measured again at 8, 16 and 24 weeks. At 24 weeks, 24 hour urine calcium will be measured again.

Any concomitant medications or adverse events will be recorded at every study visit at 4 weekly intervals.

All subjects will be assigned to receive 1g of calcium carbonate daily. Oral Cholecalciferol (powdered) will be ingested under direct supervision during study visits. Each dose of Cholecalciferol will be diluted in 10 mls of water. The Cholecalciferol used in this study is formulated as spray dried powder stabilized with DL-alpha tocopherol (dry vitamin D3 100 SD/S)(DSM Nutritional Products Switzerland Ltd).