High Bone Turnover is Associated with Low Bone Mass and Spinal Fracture in Postmenopausal Women

Abstract

A group of 366 healthy, white postmenopausal women, aged 50-81 years, mean age 66 years, were selected from the screened population of Scandinavians who were part of a multicenter study of the efficacy of tiludronate, a new bisphosphonate, in established postmenopausal osteoporosis. Eighty-eight women had a lumbar spine bone mineral density (BMD) above 0.860 g/cm2, and 278 women had a BMD below 0.860 g/cm2. Spinal fracture was diagnosed from lateral spine X-ray studies and defined as at least 20% height reduction (wedge, compression, or endplate fracture) in at least one vertebra (T4-L4). Bone resorption was assessed by measurement of the urinary excretion of type I collagen degradation products by the CrossLaps enzyme-linked immunoassay (ELISA). Bone formation was assessed by ELISA measurement of the N-terminal-midfragment as well as the intact serum osteocalcin (OCN-MID), thus omitting the influence of the instability of osteocalcin caused by the labile 6 amino acid C-terminal sequence. The women were divided into groups with high or low bone turnover according to the concentrations of urinary Cross-Laps or OCN-MID. Women in the quartiles with the highest concentrations of CrossLaps [519 +/- 119 micrograms/mmol (SD)] or OCN-MID [44.6 +/- 7.5 ng/ml (SD)] had 10-16% lower spinal BMD compared with women in the lowest quartiles (CrossLaps 170 +/- 48 micrograms/mmol (SD), and OCN-MID [22.1 +/- 3.0 ng/ml (SD)] (P< 0.0004). The prevalences of spinal fracture were 25 to 29% in the lowest quartiles, whereas the prevalences in the highest quartiles were almost double-53-54% (P < 0.006). If the women were subgrouped according to spinal BMD and prevalence of spinal fracture, corresponding results were found. Women with a BMD less than 0.860 g/cm2, without or with spinal fracture (n = 136 and n = 142), had 36-43% higher concentration of Cross-Laps (P = 0.0001) and 11-15% higher concentration of OCN-MID (P < 0.02), as compared with women with a BMD above 0.860 g/cm2 and no spinal fracture (n = 84). In conclusion, the results indicate a strong association among high bone turnover, low bone mass, and prevalence of spinal fracture, which supports the theory that high bone turnover is a risk factor for spinal fracture and osteoporosis.

Bone Resorption in Post-menopausal Women with Normal and Low BMD Assessed with Biochemical Markers Specific for Telopeptide Derived Degradation Products of Collagen Type I

“…These markers have been extensively used for both the assessment of therapeutic efficacy of antiresorptive drugs in osteoporosis and for prediction of fracture risk in postmenopausal women [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. We measured urinary and serum CTx and urinary NTx in a large cohort of untreated, healthy women stratified on the basis of their menopausal status and BMD.…”

“…Thus, biochemical markers of bone turnover provide a rapid assessment of the effects of antiresorptive therapies such as hormone replacement therapy, bisphosphonates, and calcitonin which induce a decrease in the levels of bone markers that is correlated with the long-term effect of such treatments on bone mass [5][6][7][8][9][10][11][12][13][14][15]. Due to the small annual changes in BMD, the effect of antiresorptive therapy can only be reliably monitored by BMD measurement after several years followup [5,10,13].Bone markers might also be used to prognose a high rate of bone less in postmenopausal women who would subsequently develop osteoporosis and fractures [16][17][18][19][20][21][22][23][24][25]. Bone turnover increases after menopause and remains elevated in late postmenopausal women.…”

“…Bone turnover increases after menopause and remains elevated in late postmenopausal women. It has been demonstrated that bone resorption markers are an independent predictor of fracture risk with the same predictive value as BMD measurements [19,22].In recent years, new sensitive and specific markers of …”

“…Bone markers might also be used to prognose a high rate of bone less in postmenopausal women who would subsequently develop osteoporosis and fractures [16][17][18][19][20][21][22][23][24][25]. Bone turnover increases after menopause and remains elevated in late postmenopausal women.…”

Soy isoflavone intake inhibits bone resorption and stimulates bone formation in menopausal women: meta-analysis of randomized controlled trials

“…Ravn et al (1996) observed 979 women and found that high bone turnover is associated with a significantly lower bone mass in menopausal women. Then they further indicated that high bone turnover is a risk factor for osteoporosis (Ravn et al, 1997). Harkness et al (2004) found that soy isoflavones significantly decreased bone resorption and significantly increased bone mineral density within 24 weeks.…”