Effect of Qing’e formula on circulating sclerostin levels in patients with postmenopausal osteoporosis

Abstract

Serum sclerostin is positively associated with serum 25 hydroxyvitamin D concentration. Our preliminary studies confirmed that Qing’e formula (QEF) could effectively increase serum 25 hydroxyvitamin D concentration in patients with postmenopausal osteoporosis (PMOP), but the effect of supplementation with QEF on serum sclerostin is unknown. This study investigated the effects of supplementation of QEF on serum sclerostin levels in patients with PMOP. Totally 120 outpatients and inpatients with PMOP treated in our hospital between January and October 2012 were randomly divided into QEF+calcium group, alfacalcidol+calcium group, and placebo+calcium group (n=40 each), with a follow-up period of 2 years. The serum levels of sclerostin, 25 hydroxyvitamin D, and bone turnover markers (β-CTX, N-MID and T-PINP) at baseline and at the 6th month, 1st year, 1.5th year, and 2nd year after treatment were measured. The results showed that the levels of circulating sclerostin were increased significantly at the 6th month after treatment in QEF+calcium group and alfacalcidol+calcium group as compared with placebo+calcium group (P<0.05), but there was no significant difference between the former two groups (P>0.05). The levels of β-CTX, N-MID and T-PINP in serum were decreased in both QEF+calcium group and alfacalcidol+calcium group at the 6th month after treatment, without significant difference between the two groups (P>0.05). But the levels were significantly lower than that in placebo+calcium group (P<0.05). These results suggest that the mechanism by which QEF modulates bone metabolism in patients with PMOP might be related with the effect of QEF in increasing sclerostin expression. Our findings provide a scientific rationale for using QEF as an effective drug to prevent bone loss in PMOP.

Keywords

serum sclerostin / Qing’e formula / 25 hydroxyvitamin D / bone mineral density

References

[1] FazeliPK, AckermanKE, PierceL, et al. . Sclerostin and Pref-1 have differential effects on bone mineral density and strength parameters in adolescent athletes compared with non-athletes. Osteoporos Int, 2013, 24(9): 2433-2440 PMCID: 3740025 PMID: 23579340

[2] Dawson-HughesB, HarrisSS, CegliaL, et al. . Serum sclerostin levels vary with season. J Clin Endocrinol Metab, 2014, 99(1): 149-152

[3] SzulcP, BertholonC, BorelO, et al. . Lower fracture risk in older men with higher sclerostin concentration: a prospective analysis from the MINOS study. J Bone Miner Res, 2013, 28(4): 855-864 PMID: 23165952

[4] GarneroP, Sornay-RenduE, MunozF, et al. . Association of serum sclerostin with bone mineral density, bone turnover, steroid and parathyroid hormones, and fracture risk in postmenopausal women: the OFELY study. Osteoporos Int, 2013, 24(2): 489-494 PMID: 22525978

[5] ArdawiMS, Al-KadiHA, RouziAA, et al. . Determinants of serum sclerostin in healthy pre- and postmenopausal women. J Bone Miner Res, 2011, 26(12): 2812-2822 PMID: 21812027

[6] DurosierC, Van LieropA, FerrariS, et al. . Association of circulating sclerostin with bone mineral mass, microstructure, and turnover biochemical markers in healthy elderly Men and Women. J Clin Endocrinol Metab, 2013, 98(9): 3873-3883 PMID: 23864703

[7] GennariL, MerlottiD, ValentiR, et al. . Circulating sclerostin levels and bone turnover in type 1 and type 2 diabetes. J Clin Endocrinol Metab, 2012, 97(5): 1737-1744 PMID: 22399511

[8] ModderUI, HoeyKA, AminS, et al. . Relation of age, gender, and bone mass to circulating sclerostin levels in women and men. J Bone Miner Res, 2011, 26(2): 373-379 PMCID: 3179347 PMID: 20721932

[9] Dawson-HughesB, HarrisS, CegliaL, et al. . Effect of supplemental vitamin D and calcium on serum sclerostin levels. Eur J Endocrinol, 2014, 170(4): 645-650 PMCID: 3974734 PMID: 24488080

[10] ShuaiB, ShenL, YangYP, et al. . Effects of Chinese kidney-tonifying drugs on bone mineral density (BMD), biomechanics, 25-hydroxy vitamin D3 and 1,25-dihydroxy vitamin D3 of ovariectomized osteoporosis rats. Zhongguo Gu Shang (Chinese), 2008, 21(11): 850-853

[11] ShuaiB, YangYP, ShenL, et al. . Effect of Qing’e formula on the expression of bone metabolic markers and VDR mRNA in postmenopausal osteoporosis patients. Chin Med (Chinese), 2014, 5(3): 145-152

[12] DrakeMT, SrinivasanB, ModderUI, et al. . Effects of parathyroid hormone treatment on circulating sclerostin levels in postmenopausal women. J Clin Endocrinol Metab, 2010, 95(11): 5056-5062 PMCID: 2968729 PMID: 20631014

[13] ShuaiB, YangYP, ShenL, et al. . Effect of Qing’e pill plus salvia on non-traumatic osteonecrosis of the femoral head of idiopathic type in earlier stage: a case report of a twelve-month of period. Chin Med (Chinese), 2014, 5(2): 113-117

[14] BrunkowME, GardnerJC, Van NessJ, et al. . Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet, 2001, 68(3): 577-589 PMCID: 1274471 PMID: 11179006

[15] BalemansW, EbelingM, PatelN, et al. . Increase bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet, 2001, 10(5): 537-543 PMID: 11181578

[16] Staehling-HamptonK, ProllS, PaeperBW, et al. . A 52-kb deletion in the SOST-MEOX1 intergenic region on 17q12-q21 is associated with van Buchem disease in the Dutch population. Am J Med Genet, 2002, 110(2): 144-152 PMID: 12116252

[17] BalemansW, PatelN, EbelingM, et al. . Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease. J Med Genet, 2002, 39(2): 91-97 PMCID: 1735035 PMID: 11836356

[18] LiX, OminskyMS, NiuQT, et al. . Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res, 2008, 23(6): 860-869 PMID: 18269310

[19] LiX, OminskyMS, WarmingtonKS, et al. . Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res, 2009, 24(4): 578-588 PMID: 19049336

[20] MirzaFS, PadhiID, RaiszLG, et al. . Serum sclerostin levels negatively correlate with parathyroid hormone levels and free estrogen index in postmenopausal women. J Clin Endocrinol Metab, 2010, 95(4): 1991-1997 PMCID: 2853994 PMID: 20156921

[21] XuXJ, ShenL, YangYP, et al. . Serum sclerostin levels associated with lumbar spine bone mineral density and bone turnover markers in patients with postmenopausal osteoporosis. Chin Med J (Engl), 2013, 126(13): 2480-2484

[22] MödderUI, HoeyKA, AminS, et al. . Relation of age, gender, and bone mass to circulating sclerostin levels in women and men. J Bone Miner Res, 2011, 26(2): 373-379 PMCID: 3179347 PMID: 20721932

[23] ShengZ, TongD, OuY, et al. . Serum sclerostin levels were positively correlated with fat mass and bone mineral density in Central South Chinese postmenopausal women. Clin Endocrinol, 2012, 76(6): 797-801

[24] Dawson-HughesB, HarrisSS, KrallEA, et al. . Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. New Engl J Med, 1997, 337(10): 670-676 PMID: 9278463

[25] BellidoT, AliAA, GubrijI, et al. . Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: a novel mechanism for hormonal control of osteoblastogenesis. Endocrinology, 2005, 146(11): 4577-4583 PMID: 16081646