Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study

Abstract

Introduction: Biochemical response to bisphosphonate therapy can be assessed using either a decrease in bone turnover marker beyond the least significant change (LSC) or a reduction to within a reference interval (RI). We compared the performance of these target responses and determined whether response was related to the type of bisphosphonate, compliance and baseline bone turnover markers.Methods: Biochemical responses to three oral bisphosphonates were assessed in an open, controlled trial comprising 172 postmenopausal osteoporotic women (age 53-84 years), randomized to alendronate, ibandronate or risedronate, plus calcium and vitamin D supplementation for two years. The LSC for each marker was derived within the study population whereas RIs were obtained from a control group of healthy premenopausal women (age 35-40 years).Results: Over 70% of women achieved a target response for serum CTX and PINP, irrespective of the approach used. The percentage decrease at 12 weeks was greater for women with baseline PINP above the RI -63% (difference 13%, 95%CI 0 to 27.1, P=0.049) and good compliance -67% (difference 15.9%, 95%CI 6.3 to 25.5, P=0.001). Responders had a greater increase in spine bone density compared to non-responders; for example 6.2% vs. 2.3%, (difference 3.9%, 95%CI 1.6 to 6.3, p=0.0011) for PINP LSC. The magnitude of change in bone markers was greater with ibandronate and alendronate than risedronate.Conclusions: Both approaches to response identified similar proportions of women as responders. Nonresponders had smaller increases in BMD and we suggest that biochemical assessment of response is a useful tool for the management of women with postmenopausal osteoporosis.Key words: postmenopausal osteoporosis, bone turnover markers, variability, bisphosphonate Mini Abstract (50 words)We used bone turnover markers to identify women who responded to bisphosphonate treatment for osteoporosis.Response was more likely with alendronate and ibandronate, than risedronate. There was a greater decrease in bone markers if baseline bone turnover markers were higher and if the patient took more than 80% of her medication.

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

“…Healthy premenopausal women ages 35 to 40 years were recruited to establish a premenopausal reference interval. This study population has been described elsewhere [20,21] . The women who were included had regular menstrual cycles and were vitamin D replete (25OHD >50nmol/L).…”

“…The study was conducted in accordance with ethical recommendations for monitoring adherence [23] . The 87 healthy premenopausal women were not prescribed any medication during the study [20] .…”

“…Changes in bone markers in response to treatment occur earlier and are of a greater magnitude than changes in bone density. A significant change in BMD can rarely be detected in an individual in response to oral anti-resorptive therapy in less than [18][19][20][21][22][23][24] months. Compliance with treatment is a concern in clinical practice and monitoring patients on treatment using biochemical markers can provide useful additional information for the management of patient care [14] .…”

“…Firstly the least significant change (LSC) approach which is the minimum change in bone markers that can be attributed to the treatment effect rather than random variation in the marker, or secondly a reduction in bone markers to below the mean of the reference interval (RI) for premenopausal women [10,12] . Both of these approaches can be useful to monitor the response to bisphosphonate treatment using bone markers [20] , however the use of BTM for monitoring less potent treatment may not be as informative. There are limitations to both described approaches; there is no consensus for the calculation of least significant change and the reference intervals should be appropriate and robust.…”

Biochemische Marker des Knochenstoffwechsels und ihre Bedeutung

“…PINP wird in Routinelabors bereits breiter angewandt, weil es gut reproduzierbar ist und international standardisiert wurde, so z. B. über die TRIO-Studie, bei der die Reduktion von vertebralen Frakturen parallel zur Reduktion des PINP und der antiresorptiven Biomarker (CTX) nachweisbar war [13].…”