Response of bone turnover markers to raloxifene treatment in postmenopausal women with osteopenia

Abstract

Introduction: The change in bone turnover markers (BTM) in response to osteoporosis therapy can be assessed by a decrease beyond the least significant change (LSC) or below the mean of the reference interval (RI). We compared the performance of these two approaches in women treated with raloxifene.Methods: Fifty postmenopausal osteopenic women, (age 51-72y) were randomised to raloxifene or no treatment for 2 years. Blood samples were collected for the measurement of BTM. The LSC for each marker was calculated from the untreated women and the RI obtained from healthy premenopausal women (age 35-40y). Bone mineral density (BMD) was measured at the spine and hip.Results: There was a decrease in BTM in response to raloxifene treatment; percentage change at 12 weeks, CTX -39% (95% CI -48 to -28) and PINP -32% (95% CI -40 to -23) P<0.001. The proportion of women classified as responding to treatment using LSC at 12 weeks was: CTX 38%, PINP 52%, at 48 weeks CTX 60%, PINP 65%. For the RI approach; at 12 weeks CTX and PINP 38%, at 48 weeks CTX 40%, PINP 45%. There was a significant difference in the change in spine BMD in the raloxifene treated group compared to the no-treatment group at week 48; difference 0.031 g/cm2, (95% CI 0.016 to 0.046, P<0.001).Conclusions: The two approaches identified women that reached the target for treatment using BTM.Both LSC and RI criteria appear useful in identifying treatment response but the two approaches do not fully overlap and may be complementary.

Urinary N‐Telopeptide as Predictor of Onset of Menopause‐Related Bone Loss in Pre‐ and Perimenopausal Women

“…(14) We used modified Poisson regression instead of logistic regression because bone loss is not a rare outcome in this group and because the former approach is more robust to model misspecification. (13) Separate analyses were conducted for LS bone loss and FN bone loss, each defined using two BMD decline rate thresholds (as described above).…”

“…The first was the site‐specific least significant change (LSC) in BMD divided by the median number of intervening years between BMD measurements in the study sample. The LSC for a measure depends on the precision error in its measurement and is the smallest amount of change that would be statistically significantly different from no change at 2‐sided type I error (alpha) of 5% . The LSC is recommended for defining whether a true physiologic change in BMD has occurred in clinical practice and is calculated as 2.77 times the CV for the measurement .…”

“…We used multivariable modified Poisson regression with U‐NTX at SWAN baseline as primary predictor and significant bone loss (yes/no) from time of U‐NTX measurement to 3 to 4 years later as outcome and adjusted for MT stage (pre‐ versus early perimenopause), age, race/ethnicity (white, African American, Chinese, Japanese), BMI, urine collection time (to account for diurnal variation in bone turnover markers), starting BMD, and study site as covariates and robust estimation of standard error . We used modified Poisson regression instead of logistic regression because bone loss is not a rare outcome in this group and because the former approach is more robust to model misspecification . Separate analyses were conducted for LS bone loss and FN bone loss, each defined using two BMD decline rate thresholds (as described above).…”

“…The LSC for a measure depends on the precision error in its measurement and is the smallest amount of change that would be statistically significantly different from no change at 2-sided type I error (alpha) of 5%. (10,12,13) The LSC is recommended for defining whether a true physiologic change in BMD has occurred in clinical practice and is calculated as 2.77 times the CV for the measurement. (10) In SWAN, each of the five Bone Cohort sites performed duplicate BMD measurements at the LS and FN in five women, with complete repositioning (25 duplicate measurements in total).…”

DIAGNOSIS OF ENDOCRINE DISEASE: Bone turnover markers: are they clinically useful?

“…Even so, their effect can be monitored using BTM. In 60-65% of women with osteopenia, a significant response could be demonstrated using the LSC approach with CTX or PINP (34). The BTM response to raloxifene was greatest in those with greatest adherence (35) providing further support for use of BTM as a means of identifying poor adherence to therapy (see below).…”