HYPOVITAMINOSIS D IN INDIAN FEMALES WITH POSTMENOPAUSAL OSTEOPOROSIS DR. SHAH WALIULLAH 1 DR. VINEET SHARMA 2 DR. R N SRIVASTAVA 3 DR. YASHODHARA PRADEEP 4 DR. A A MAHDI 5 DR. SANTOSH KUMAR 6 1 Research Fellow, Dept. of Orthopaedic Surgery, King George Medical University, Lucknow, India 2 Professor & Head, Dept. of Orthopaedic Surgery, King George Medical University, Lucknow, India 3 Professor & Head, Dept. of Physical Medicine & Rehabilitation, King George Medical University, Lucknow, India 4 Professor, Dept. of Obstretics and Gynaecology, King George Medical University, Lucknow, India 5 Professor & Head, Dept. of Biochemistry, King George Medical University, Lucknow, India 6 Professor, Dept. of Orthopaedic Surgery, King George Medical University, Lucknow, India ABSTRACT Vitamin D is a fat soluble hormone that plays a vital role in calcium homeostasis. Estrogen increases serum levels of 1,25 (OH )2D and calcium, thereby affecting calcium metabolism.due to deficiency of estrogen after menopause in females, there is increase in osteoclastic cell activity resulting in decrease bone quality and bone mineral density. We carried out this cross sectional cohort study to find out the prevalence of Vit D in postmenopausal women having low bone mineral density. Total 128 females with established menopause were enrolled in study. All female had osteoporosis of at least one side either at spine, hip or at forearm. 25(OH)D level in the serum were measured in all patients by chemiluminiscence immunoassay and graded into three groups as Vitamin D deficiency( < 20ng/ml), Vitamin D insufficiency(21 29ng/ml), and sufficiency(30 100ng/ml). The results are presented in means and percentages. All the analysis was carried out by using SPSS 16.0 version. A total of 128 females were included in the study with mean age of 54.35 (±4.80) years and range between 45 to 65 years. The average no. of years since menopause was 6.05 (±4.31) years. Out of 128 subjects only 21(16.45%) subjects had sufficient level of Vit D, 40 (31.2%) subjects had insufficient Vit D level and rest 67 (52.3%)subjects had deficient Vit D level. There is high prevalence of Vit D deficiency among post menopausal osteoporotic females as only less than a quarter of our patients have adequate Vit D level, we recommend that all post menopausal female with osteoporosis should undergo evaluation and treatment for Vit D deficiency for the optimum management of osteoporosis. KEYWORDS: Post Menopausal Osteoporosis, Vitamin D Deficiency, Vitamin D Insufficiency, Vitamin D Sufficiency 448
INTRODUCTION Vitamin D3 (Cholecalciferol) is synthesized in the skin, from 7 dehydro-cholesterol in the presence of UVB rays. Cholecalciferol undergo further hydroxylation in the liver and subsequently in kidney to convert into the active form 1,25 dihydroxy cholecalciferol responsible for a multitude of its effects(1). There is the recent surge in the literature regarding vitamin D and its correlation to multiple diseases, because of its anti-inflammatory and immune-modulating properties, it has been linked to cardiovascular disease, diabetes, skin cancer, multiple sclerosis, cognition disorder apart from musculoskeletal disorders(1,2). Vitamin D (Vit D) is a fat soluble hormone that plays a vital role in calcium homeostasis. Due to deficiency of Vit D, there is a decrease in absorption of calcium from the intestine resulting in a decrease level of serum ionized calcium and up regulation of parathyroid gland, causing secondary hyperparathyroidism. Secondary hyperparathyroidism increases serum calcium by mobilizing bone calcium, results in bone loss(3). Postmenopausal osteoporosis in females is due to deficiency of estrogen following either due to surgical or natural menopause. Estrogen is responsible for controlling osteoclastic cell activity and bone health. Due to deficiency of estrogen there is increase in the number of osteoclast cell and osteoclastic activity. Estrogen increases serum 1,25 (OH )2D by stimulating renal 1-hydroxylase enzyme,thereby help in maintaing calcium homeostasis and bone turn over metabolism, so in postmenopausal osteoporosis due to deficiency of estrogen there is also decline in the level of active Vit D(4). We carried out this cross sectional cohort study to find out the prevalence of Vit D in postmenopausal women having low bone mineral density. Methods & Material: Total 128 females were recruited from outdoor department of Orthopaedic surgery and Obstetrics and gynaecology, in study. All bio-chemical analysis were done in department of Biochemistry. Informed consent was taken from each patient and ethical clearance was approved by Institutional Ethical Committee. All female had menopause, with minimum one year passed from the cessation of menstruation and they had osteoporosis of at least one side either at spine, hip or at forearm as per bone mineral density(bmd) done by Dual Energy X- ray Absorptiometry (DEXA) scan. All patients were classified according to WHO grading system in normal, osteopenic and osteoporosis depending upon their T scores(5). Patients having systemic metabolic disorder like liver disorder, renal dysfunction and intestinal malfunction affecting calcium and Vit D metabolism,malignancy, thyroidism and hyperparathyroidism were excluded. Patients who were previously treated for Vit D 449
deficiency or having any long term medication were also excluded. 25(OH)D level in the serum were measured in all patients by chemiluminiscence immunoassay. Patients were graded into three groups as Vitamin D deficiency if level of 25(OH)D less than 20ng/ml, Vitamin D insufficiency if level of 25(OH)D found between 21 29ng/ml, and sufficiency if level of 25(OH)D found between 30 100ng/ml(2,6). Statistical analysis: The results are presented in means and percentages. The one way analysis of variance (ANOVA) was used to compare the vitamin D level and BMD among normal, osteopenia and osteoporosis. The Tukey s post hoc multiple comparison test was used to compare between two groups which were found to be statistically significant in ANOVA at p<0.05. The unpaired t-test was used to compare vitamin D level and BMD between two groups. The p- value <0.05 was considered significant. All the analysis was carried out by using SPSS 16.0 version (Chicago, Inc., USA). Results: A total of 128 females were included in the study with mean age of 54.35 (±4.80) years and range between 45 to 65 years. The average no. of years since menopause was 6.05 (±4.31) years. Out of 128 subjects only 21(16.45%) subjects had sufficient level of Vit D, 40 (31.2%) subjects had insufficient Vit D level and rest 67 (52.3%)subjects had deficient Vit D level(fig-1). Fig.1: Vitamin D status among all the women Mean bone mineral density in 128 patients with osteoporosis at spine was 0.73±0.12,at hip 0.62±0.07 and at left forearm 0.58±0.16.Mean T score in 128 patients with osteoporosis at spine was -3.76±0.97,at left hip -2.9±0.53,at right hip -2.96±0.57 and at left forearm- 3.5±1.7.There was no significant difference in the vitamin D level among patients having either normal, osteopenia or osteoporosis at spine,hip and forearm region(table-1). 450
Table:1 Comparison of Vitamin D levels between different groups Vitamin D level p-value 1 (Mean±SD) Normal Osteopenia Osteoporosis T-spine 22.80±0.00 16.35±5.46 21.16±12.72 0.35 a Neck 23.30±0.00 18.12±8.10 21.43±13.09 0.29 a Forearm 26.50±3.40 22.24±9.68 20.39±12.34 0.58 b a Unpaired t-test between Osteopenia and Osteoporosis, b ANOVA test DISCUSSION Vit D deficiency is a global health problem and it is widely prevalent in India affecting all age groups(2). We observed high prevalence of Vit D deficiency in post menopausal osteoporotic patients in our study. We found only 16.45% patients had sufficient Vit D levels, 31% had insufficient Vit D levels and rest 52% had deficient Vit D levels. Sufficient Vit D levels signifies that serum 25(OH )D level is above 30ng/ml, at this level intestinal absorption of calcium is optimum under Vit D action and level of parathyroid hormone falls in serum, thus preventing secondary hyperparathyroidism, responsible for mobilizing bone calcium into serum. At level below 20 ng/ml, there is decrease calcium absorption from gut and increase in parathyroid level resulting into secondary hyperparathyroidism and further bone loss(2,7). Narula et al(8) in his study on post menopausal osteoporotic females reported that 62% females were having deficient Vit D levels. Harinarayan et al(9) reported higher prevalence, 70% post menopausal females subjects had deficient Vit D levels and 23% subjects had insufficient level. Osteoporosis occur due to imbalance in bone turn over metabolism,characterized by increase osteoclastic activity in comparison to osteoblastic activity, resulting into detoriation of bone quality and decrease in bone mineral density. Vit D plays an integral role in bone turnover metabolism by affecting calcium and parathyroid hormone activity. In postmenopausal osteoporosis, due to deficiency of estrogen, there is decrement in the level of active 1,25 (OH )2D because of less stimulation of renal 1-hydroxylase enzyme, results into decrease calcium absorption from gut and consequently secondary hyperparathyroidism(4). Post menopausal osteoporosis can be effectively treated by early diagnosis and treatment by biphosphonate, calcium and Vit D supplementation(7,9,10). In our study we treated our subjects with weekly or monthly biphosphonate,1250 mg calcium per day and 60,000 IU of vitamin D weekly for ten weeks followed by maintenance dose of 1000 IU per day. 451
CONCLUSION There is high prevalence of Vit D deficiency among post menopausal osteoporotic females as only less than a quarter of our patients have adequate Vit D level, we recommend that all post menopausal female with osteoporosis should undergo evaluation and treatment for Vit D deficiency for the optimum management of osteoporosis. Conflict of Intrest: None REFERENCES 1. Kulie T, Groff A, Redmer J, Hounshell J, Schrager S. Vitamin D: An Evidence-Based Review. J Am Board Fam Med 2009;22:698 706. 2. Ritu G, Gupta A.Vitamin D Deficiency in India: Prevalence, Causalities and Interventions. Nutrients 2014, 6, 729-77 3. Gallagher JC, Riggs BL, DeLuca HF.Effect of estrogen on calcium absorption and serum vitamin D metabolites in postmenopausal osteoporosis. J Clin Endocrinol Metab. 1980 Dec; 51 (6): 1359-64. 4. Sipos W, Pietschmann P, Rauner M, Schindl K K, Patsch J.Pathophysiology of osteoporosis. Wien Med Wochenschr (2009) 159/9 10: 230 234 5. Kanis JA. (1994). Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int., 4(6): 368-81. 6. Holick MF.Optimal vitamin D status for the prevention and treatment of osteoporosis. Drugs Aging. 2007;24(12):1017-29. 7. Watts NB, Bilezikian JP, Camacho PM, Greenspan SL, Harris ST, Hodgson SF, Kleerekoper M, Luckey MM, McClung MR, Pollack RP, Petak SM; AACE Osteoporosis Task Force.American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of postmenopausal osteoporosis. Endocr Pract. 2010 Nov-Dec;16 Suppl 3:1-37 8. Narula R, Mujtaba T, Iraqi A A, Agarwal K, Agarwal A, Arya A. Vitamin D Deficiency Among Postmenopausal Women with Osteoporosis Journal of Clinical and Diagnostic Research. 2013 February, Vol-7(2): 336-33 9. Harinarayan Cv, Alok Sachan, P. Amaresh reddy, et al. vitamin D status and bone mineral Density in Women of reproductive and Postmenopausal age groups: A cross-sectional study from South India. J Assoc Physicians India 2011;59:695-701. 10. Frederick T. Murphy,Alan J. Kivitz, Earl E. Sands,Management of Postmenopausal Osteoporosis. J Am Osteopath Assoc October 2003;103( 6 ):6-11 11. Delmas PD.Treatment of postmenopausal osteoporosis. Lancet 2002; 359: 2018 26 452