Early changes in biochemical markers of bone turnover and their relationship with bone mineral density changes after 24 months of treatment with teriparatide

Abstract

SummaryWe report the changes in biochemical markers of bone formation during the first 6 months of teriparatide therapy in postmenopausal women with osteoporosis according to previous antiresorptive treatment. Prior therapy does not adversely affect the response to teriparatide treatment. Similar bone markers levels are reached after 6 months of treatment.IntroductionThe response of biochemical markers of bone turnover with teriparatide therapy in subjects who have previously received osteoporosis drugs is not fully elucidated. We examined biochemical markers of bone formation in women with osteoporosis treated with teriparatide and determined: (1) whether the response is associated with prior osteoporosis therapy, (2) which marker shows the best performance for detecting a response to therapy, and (3) the correlations between early changes in bone markers and subsequent bone mineral density (BMD) changes after 24 months of teriparatide.MethodsWe conducted a prospective, open-label, 24-month study at 95 centers in 10 countries in 758 postmenopausal women with established osteoporosis (n = 181 treatment-naïve) who had at least one post-baseline bone marker determination. Teriparatide (20 μg/day) was administered for up to 24 months. We measured procollagen type I N-terminal propeptide (PINP), bone-specific alkaline phosphatase (b-ALP), and total alkaline phosphatase (t-ALP) at baseline, 1 and 6 months, and change in BMD at the lumbar spine, total hip and femoral neck from baseline to 24 months.ResultsSignificant increases in formation markers occurred after 1 month of teriparatide regardless of prior osteoporosis therapy. The absolute increase at 1 month was lower in previously treated versus treatment-naïve patients, but after 6 months all groups reached similar levels. PINP showed the best signal-to-noise ratio. Baseline PINP correlated positively and significantly with BMD response at 24 months.ConclusionsThis study suggests that the long-term responsiveness of bone formation markers to teriparatide is not affected in subjects previously treated with antiresorptive drugs.

A Fracture Does Not Adversely Affect Bone Mineral Density Responses after Teriparatide Treatment

“…These findings were similar to previous reports of teriparatide's effects on BMD in patients with a history of antiresorptive therapy [10] (Table 6). The percent changes of BMD in our patients with prolonged bisphosphonate treatment of approximately 4 to 5 years were comparable to those of studies that reported the effect of teriparatide in patients who received a shorter duration of antiresorptive medication [5,16] (Table 6).…”

Systematic review of the use of bone turnover markers for monitoring the response to osteoporosis treatment: the secondary prevention of fractures, and primary prevention of fractures in high-risk groups

“…5,6,11,15,34,47,50, Sixteen of the full papers were published in languages other than English. 37,52,74,76,79,81,95,[97][98][99][100][101][102][103][104][105] Nineteen studies had duplicate publications; where this was the case 14,40,42,43,56,103,104, one paper was allocated as the primary publication (full paper if the duplicate was an abstract or letter; the published paper if the duplicate comprised data from the manufacturer's online trials database, the most recent publication, or the paper published in English) and used as the citation for the study throughout the review; 14,40,42,43,56,106,[131][132][133][134][135][136][137][138][139][140]142,143 relevant data were extracted from all publications where applicable. After full-paper screening, 42 studies (across 70 publications) met the inclusion criteria for the review of clinical effectiveness; the flow of studies through the review is given in Figure 1<...>…”

“…Changes in bone turnover rates have been detected in post-menopausal women within as early as 2 weeks after starting HRT, 42 although the peak accuracy of changes in bone turnover markers to predict fracture risk in response to osteoporosis treatment may be later than this, between 3 and 12 months after initiating treatment, depending on the treatment and bone turnover marker used. [43][44][45][46] The ability to identify non-responders early within the treatment can be beneficial for patients by allowing early changes in management strategy if deemed necessary.…”

Factores relacionados con la respuesta inadecuada al tratamiento osteoformador (teriparatida/PTH 1-84) en pacientes con osteoporosis severa: resultados preliminares

“…As noted previously, several studies point to the role of bone remodeling markers 8,9,11,12,15,16,19 to predict the level of response to long-term bone forming treatment 9,12,19 , especially when the PINP bone formation marker is used 12,16 . In a post-hoc study, Eastell et al 13 note that by quantifying the change in PINP at 3 months of starting teriparatide treatment allowed for the indentification of long-term patients who presented a significant BMD increase, particularly if the increase was greater than 10 ng/mL 9,[12][13][14][15][16] .…”