Effect of Teriparatide Treatment on Circulating Periostin and Its Relationship to Regulators of Bone Formation and BMD in Postmenopausal Women With Osteoporosis

Abstract

Context: Treatment of postmenopausal osteoporosis with teriparatide parathyroid hormone amino terminal 1-34 increases bone formation and improves bone microarchitecture. A possible modulator of action is periostin. In vitro experiments have shown that periostin might regulate osteoblast differentiation and bone formation through Wnt signaling. The effect of teriparatide on periostin is not currently known.

Objectives: To determine the effect of teriparatide treatment on circulating levels of periostin and other regulators of bone formation and investigate how changes in periostin relate to changes in bone turnover markers, regulators of bone formation, and bone mineral density (BMD).

Participants and design: Twenty women with osteoporosis; a 2-year open-label single-arm study.

Intervention: Teriparatide 20 µg was administered by subcutaneous injection daily for 104 weeks. Periostin, sclerostin, and Dickkopf-related protein 1, procollagen type I N-terminal propeptide (PINP), and C-telopeptide of type I collagen were measured in fasting serum collected at baseline (two visits) and then at weeks 1, 2, 4, 12, 26, 52, 78, and 104. BMD was measured at the lumbar spine, total hip, and femoral neck using dual energy x-ray absorptiometry.

Results: Periostin levels increased by 6.6% [95% confidence interval (CI), -0.4 to 13.5] after 26 weeks of teriparatide treatment and significantly by 12.5% (95% CI, 3.3 to 21.0; P < 0.01) after 52 weeks. The change in periostin correlated positively with the change in the lumbar spine BMD at week 52 (r = 0.567; 95% CI, 0.137 to 0.817; P < 0.05) and femoral neck BMD at week 104 (r = 0.682; 95% CI, 0.261 to 0.885; P < 0.01).

Conclusions: Teriparatide therapy increases periostin secretion; it is unclear whether this increase mediates the effect of the drug on bone.

Trial registration: ClinicalTrials.gov NCT01293292.

Figures

Figure 1.

The precision profile of the assay showing the percentage of the coefficient of variation at different concentrations of periostin.

Figure 2.

Changes in serum circulating levels of periostin over a 104-week treatment period with teriparatide. Data presented as the mean percentage of change and 95% CI from baseline (0) (n = 20) at several time points. *P < 0.05; **P < 0.01.

Figure 3.

Changes in serum circulating levels of (left) sclerostin and (right) DKK-1 over a 104-week treatment period with teriparatide. Data presented as mean percentage of change and 95% CI from baseline (0) (n = 20) at several time points. *P < 0.05 compared with baseline.

Figure 4.

Graphs showing changes between periostin and DKK-1, sclerostin, total hip BMD, and femoral neck BMD.