Changes In Markers Of Formation Research Articles

Consistency of Bone Turnover Marker and Calcium Responses to Parathyroid Hormone (1–84) Therapy in Postmenopausal Osteoporosis

We investigated whether those who experience the greatest increases in bone turnover in response to parathyroid hormone (PTH) therapy are the same as those who experience elevations in calcium levels. Baseline and follow-up procollagen type I N propeptide (PINP), bone-specific alkaline phosphatase (BAP), C-terminal telopeptide (CTX), and serum and urinary calcium levels were analyzed post hoc from the 119 postmenopausal women with osteoporosis randomized to PTH(1–84) in the Parathyroid Hormone and Alendronate trial. Short-term changes in the markers of bone turnover were highly correlated with one another ( r = 0.57–0.87, p < 0.001). In contrast, change in serum calcium correlated only modestly with changes in markers of formation ( r = 0.22–0.30, p ≤ 0.02) and did not correlate significantly with change in CTX ( r = 0.13, p = 0.18). Participants who experienced hypercalcemia experienced greater 3-mo changes in BAP than those who did not (78% vs. 42% increase in BAP, p = 0.04), with similar trends for PINP and CTX. In conclusion, the use of 1 marker of bone turnover, rather than multiple markers, may be sufficient to assess biochemical response to PTH(1–84). The relationship between bone turnover marker and calcium responses to PTH(1–84) is modest and does not suggest a profound, broadly heightened responsiveness of certain individuals to therapy.

Hetereogeneity in skeletal response to full-length parathyroid hormone in the treatment of osteoporosis

In the PaTH trial, among the 119 women randomized to parathyroid hormone PTH(1-84) and 60 to alendronate, we found much greater variation in BMD and markers in response to PTH(1-84) compared to alendronate. No baseline participant characteristic consistently predicted increased bone density response to PTH(1-84), although women with larger changes in 1,25 dihydroxyvitamin D during therapy had larger increases in BMD. We examined variability in BMD and markers of bone turnover in response to treatment with PTH(1-84) or alendronate in the PaTH trial. Differences in SD were examined using Levine's test for homogeneity of variance. Change in BMD across quartiles of participant characteristics was examined using ANOVA. We found much greater variation in response to PTH(1-84) compared to alendronate. The SD for change in cancellous spine BMD (by QCT) was 32% on PTH(1-84) compared to 13% on alendronate (p < 0.0001). The higher variability in the PTH(1-84) group was due to substantial numbers of women with large increases in BMD on PTH(1-84). Similarly, the SD of changes in markers of formation and resorption were significantly higher on PTH(1-84) than on ALN. No baseline participant characteristics predicted increased bone density response to PTH(1-84) therapy. However, change in 1,25-OH(2)D explained 16% of the variance in BMD response to PTH(1-84). There is significant variability in the skeletal response to PTH(1-84), which exceeds that observed with alendronate. Changes in 1,25-OH(2)D were related to larger gains in BMD. This finding may have implications for elucidating either the pathway by which PTH affects the skeleton or traits that result in particular responsiveness to PTH therapy.