Effects of High and Low Doses of Folic Acid on the Soluble Receptor Activator of Nuclear Factor-kappa B Ligand/Osteoprotegerin Ratio during Pregnancy
-
Nazila FATHI MAROUFI
,
Amir GHORBANIHAGHJO
,
Manizheh SAYYAH MELLI
,
Maryam VAEZI
,
Zohreh HEKMATI AZAR MEHRABANI
,
Maryam BANNAZADEH AMIRKHIZ
,
Nadereh RASHTCHIZADEH
Abstract
Background: Pregnancy Associated Osteoporosis (PAO) can lead to serious difficulties such as fragility fractures, elongated back pain and height loss in affected women. Soluble Receptor Activator of Nuclear Factor-Kappa B ligand (sRANKL) to Osteoprotegerin (OPG) ratio is chosen as a bone metabolism equation in many bone diseases characterized by bone resorption, such as post-menopausal osteoporosis and would be modified with folic acid supplementation. This study was done to compare the effects of high dose (5mg/day) and low dose (0.5 mg/day) folic acid in the RANKL/OPG ratio and Tumor Necrosis Factorα (TNFα) concentration during pregnancy.
Methods: Forty-five pregnant women who visited the AL-Zahra Hospital, Tabriz Iran, from September 2013 to November 2014 were assigned into two groups in this randomized, double-blind, clinical trial, included women who took 5 mg/day (group1) and who took 0.5 mg/day (Group 2) folic acid supplementation before pregnancy until 36th pregnancy. The biochemical variables in serum of pregnant women were measured before and at the end of the study. The study was registered in the Iranian Registry of Clinical Trials (IRCT) as ID, IRCT2013122315903N1.
Results: OPG levels were significantly higher compared with the baseline value (P=0.008), although sRANKL (P<0.001), TNFα (P=0.005) and sRANKL/OPG ratio (P<0.001) reduced significantly with high dose of folic acid supplementation. A significant positive correlation was observed between the decreased RANKL and TNFα levels (r=0.451, P=0.031) at the end of study in high dose group.
Conclusion: High dose of folic acid supplementation could decrease bone resorptive biomarkers and may prevent PAO in pregnant women by increasing OPG and decreasing sRANKL and TNFα.
Cundy T, Kanis JA (1981). Calcium homoeostasis during pregnancy. Br Med J (Clin Res Ed), 283: 562–563.
Givens MH, Macy IG (1933). The chemical composition of the human fetus. J Biol Chem, 102:7-17.
More C, Bhattoa HP, Bettembuk P, Balogh A (2003). The effects of pregnancy and lactation on hormonal status and biochemical markers of bone turnover. Eur J Obstet Gynecol Reprod Biol, 106:209-213.
Seki K, Makimura N, Mitsui C, Hirata J, Nagata I (1991). Calcium-regulating hormones and osteocalcin levels during pregnancy: a longitudinal study. Am J Obstet Gynecol, 164:1248-1252.
Cross NA, Hillman LS, Allen SH, Krause GF, Vieira NE (1995). Calcium homeostasis and bone metabolism during pregnancy, lactation, and postweaning: a longitudinal study. Am J Clin Nutr, 61:514-523.
Sowers M, Scholl T, Harris L, Jannausch M (2000). Bone loss in adolescent and adult pregnant women. Obstet Gynecol, 96:189-193.
Pearson D, Kaur M, San P, Lawson N, Baker P, Hosking D (2004). Recovery of pregnancy mediated bone loss during lactation. Bone, 34:570-578.
Promislow JH, Hertz-Picciotto I, Schramm M, Watt-Morse M, Anderson JJ (2004). Bed rest and other determinants of bone loss during pregnancy. Am J Obstet Gynecol, 191:1077-1083.
Kovacs CS, Kronenberg HM (1997). Maternal-Fetal Calcium and Bone Metabolism During Pregnancy, Puerperium, and Lactation 1. Endocr Rev, 18:832-872.
Affinito P, Tommaselli GA, di Carlo C, Guida F, Nappi C (1996). Changes in bone mineral density and calcium metabolism in breastfeeding women: a one year follow-up study. J Clin Endocrinol Metab, 81:2314-2318.
Black A, Topping J, Durham B, Farquharson R, Fraser W (2000). A detailed assessment of alterations in bone turnover, calcium homeostasis, and bone density in normal pregnancy. J Bone Miner Res, 15:557-563.
Boyce BF, Xing L (2008). Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys, 473:139-146.
Boyce BF, Xing L (2007). Biology of RANK, RANKL, and osteoprotegerin. Arthritis Res Ther, 1:S1.
Hong J-S, Santolaya-Forgas J, Romero R, Espinoza J, Gonçalves LF, Kim YM, Edwin S, Yoon BH, Nien JK, Hassan S (2005). Maternal plasma osteoprotegerin concentration in normal pregnancy. Am J Obstet Gynecol, 193:1011-1015.
Silva I, Branco J (2011). Rank/Rankl/opg: literature review. Acta Reumatol Port, 36:209-218.
Eghbali-Fatourechi G, Khosla S, Sanyal A, Boyle WJ, Lacey DL, Riggs BL (2003). Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J Clin Invest, 111:1221-30.
Sasaki N, Kusano E, Ando Y, Yano K, Tsuda E, Asano Y (2001). Glucocorticoid decreases circulating osteoprotegerin (OPG): possible mechanism for glucocorticoid induced osteoporosis. Nephrol Dial Transplant, 16:479-482.
Naylor K, Rogers A, Fraser R, Hall V, Eastell R, Blumsohn A (2003). Serum osteoprotegerin as a determinant of bone metabolism in a longitudinal study of human pregnancy and lactation.J Clin Endocrinol Metab, 88:5361-5365.
Uemura H, Yasui T, Kiyokawa M, Kuwahara A, Ikawa H, Matsuzaki T, Maegawa M, Furumoto H, Irahara M (2002). Serum osteoprotegerin/osteoclastogenesis-inhibitory factor during pregnancy and lactation and the relationship with calcium-regulating hormones and bone turnover markers. J Endocrinol, 174:353-359.
Yano K, Shibata O, Mizuno A, Kobayashi F, Higashio K, Morinaga T, Tsuda E (2001). Immunological study on circulating murine osteoprotegerin/osteoclastogenesis inhibitory factor (OPG/OCIF): possible role of OPG/OCIF in the prevention of osteoporosis in pregnancy. Biochem Biophys Res Commun, 288:217-224.
Xian CJ, Cool JC, Scherer MA, Fan C, Foster BK (2008). Folinic acid attenuates methotrexate chemotherapy‐induced damages on bone growth mechanisms and pools of bone marrow stromal cells. J Cell Physiol, 214:777-785.
Morris MS, Jacques PF, Selhub J (2005). Relation between homocysteine and B-vitamin status indicators and bone mineral density in older Americans. Bone, 37:234-242.
Sato Y, Honda Y, Iwamoto J, Kanoko T, Satoh K (2005). Effect of folate and mecobalamin on hip fractures in patients with stroke: a randomized controlled trial. JAMA, 293:1082-1088.
Hossein-nezhad A, Mirzaei K, Maghbooli Z, Najmafshar A, Larijani B (2011). The influence of folic acid supplementation on maternal and fetal bone turnover. J Bone Miner Metab, 29:186-192.
Lam J, Takeshita S, Barker JE, Kanagawa O, Ross FP, Teitelbaum SL (2000). TNF-α induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand. J Clin Invest, 106:1481-8.
Sarıkaya S, Özdolap Ş, Açıkgöz G, Erdem CZ (2004). Pregnancy-associated osteoporosis with vertebral fractures and scoliosis. Joint Bone Spine, 71:84-85.
Tran H, Petrovsky N (2002). Pregnancy‐associated osteoporosis with hypercalcaemia. Intern Med J, 32:481-485.
Anai T, Tomiyasu T, Arima K, Miyakawa I (1999). Pregnancy‐Associated Osteoporosis with Elevated Levels of Circulating Parathyroid Hormone‐Related Protein: A Report of Two Cases. J Obstet Gynaecol Res, 25:63-67.
Choe EY, Song JE, Park KH, Seok H, Lee EJ, Lim S-K, Rhee Y (2012). Effect of teriparatide on pregnancy and lactation-associated osteoporosis with multiple vertebral fractures. J Bone Miner Metab, 30:596-601.
Kalkwarf HJ, Specker BL (2002). Bone mineral changes during pregnancy and lactation. Endocrine, 17:49-53.
Yamaga A, Taga M, Takahashi T, Shirai T (2000). A case of postpregnancy osteoporosis. Eur J Obstet Gynecol Reprod Biol, 88:107-109.
Yamamoto N, Takahashi H, Tanizawa T, Kawashima T, Endo N (1994). Bone mineral density and bone histomorphometric assessments of postpregnancy osteoporosis: a report of five patients. Calcif Tissue Int, 54:20-25.
Di Gregorio S, Danilowicz K, Rubin Z, Mautalen C (2000). Osteoporosis with vertebral fractures associated with pregnancy and lactation. Nutrition, 16:1052-1055.
O’sullivan S, Grey A, Singh R, Reid I (2006). Bisphosphonates in pregnancy and lactation-associated osteoporosis. Osteoporos Int, 17:1008-1012.
Klejna K, Naumnik B, Gasowska K, Myśliwiec M (2009). OPG/RANK/RANKL signaling system and its significance in nephrology. Folia Histochem Cytobiol, 47:199-206.
Wei S, Kitaura H, Zhou P, Ross FP, Teitelbaum SL (2005). IL-1 mediates TNF-induced osteoclastogenesis. J Clin Invest, 115:282-90.
Weitzmann MN (2013). The role of inflammatory cytokines, the RANKL/OPG axis, and the immunoskeletal interface in physiological bone turnover and osteoporosis. Scientifica, 2013:125705.
Zhang Y-H, Heulsmann A, Tondravi MM, Mukherjee A, Abu-Amer Y (2001). Tumor necrosis factor-α (TNF) stimulates RANKL-induced osteoclastogenesis via coupling of TNF type 1 receptor and RANK signaling pathways. J Biol Chem, 276:563-568.
| Files | ||
| Issue | Vol 46 No 4 (2017) | |
| Section | Original Article(s) | |
| Keywords | ||
| Folic acid Osteoprotegerin Tumor necrosis factorα Pregnancy | ||
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