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

Department of Clinical Biochemistry, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
Osteoporosis International (Impact Factor: 4.17). 10/2010; 22(6):1935-46. DOI: 10.1007/s00198-010-1379-y
Source: PubMed


We 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.
The 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.
We 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.
Significant 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.
This study suggests that the long-term responsiveness of bone formation markers to teriparatide is not affected in subjects previously treated with antiresorptive drugs.

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    • "Thus, reduced bone metabolism due to a lower basal metabolic ratio is a possible risk factor for fracture in postmenopausal women with T2D. Furthermore, markers for bone turnover can be used to evaluate the efficacy of a drug during osteoporosis treatment, although diabetes also may alter bone metabolism, which then may affect bone turnover markers [19] [20]. "
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    ABSTRACT: Objective: Diabetes is a risk factor for osteoporosis, and glycemic control is critical during osteoporosis treatment in patients with type 2 diabetes (T2D). However, diabetic therapies have potentially adverse effects on bone metabolism. Additionally, biomarkers for bone metabolism are directly affected by drug therapies for osteoporosis. This study examined resting energy expenditure (REE) and respiratory quotient (RQ) as indices of bone metabolism in postmenopausal Japanese women with T2D. Methods: Forty-six postmenopausal Japanese women with T2D were examined. Procollagen type 1 N-terminal propeptide (P1NP, a fasting serum bone formation marker) and carboxy-terminal collagen cross-links-1 (CTX-1, a resorption marker) were evaluated, along with intact parathyroid hormone, 25-hydroxyvitamin D (25[OH]D), urine microalbumin, motor nerve conduction velocity, sensory nerve conduction velocity, R-R interval, body composition, REE, RQ, and bone mineral density at the nondominant distal radius. Results: The mean T-score was low with high variance (-1.7 ± 1.6), and 18 patients (39%) met the criteria for osteoporosis. REE was positively correlated with body mass index (β = 0.517; r2 = 0.250), serum calcium (β = 0.624; r2 = 0.200), glycated hemoglobin A1C for the previous 6 mo (β = 0.395; r2 = 0.137), and the serum P1NP/CTX-1 ratio (β = 0.380; r2 = 0.144). RQ was positively correlated with serum 25(OH)D (β = 0.387; r2 = 0.131). Conclusion: The basal metabolic rate and diabetic pathophysiology are interrelated with bone turnover.
    No preview · Article · Jun 2015 · Journal of Nutrition
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    • "Previous studies have shown an association between changes in bone turnover markers and fracture incidence/risk in postmenopausal women treated with antiresorptive therapies, including alendronate [7], risedronate [19, 45] and raloxifene [5, 6, 8], but not with strontium ranelate [46] or zoledronic acid [15]. Researchers from the EUROFORS trial reported the lack of a significant relationship between changes in biochemical markers and fracture risk in postmenopausal women treated with teriparatide [18]. However, these results should be interpreted with caution given the low number of subjects with incident fractures during the course of the study, and the lack of power to detect any potential correlations. "
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    ABSTRACT: Changes of the bone formation marker PINP correlated positively with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis (GIO) who received 18-month treatment with teriparatide, but not with risedronate. These results support the use of PINP as a surrogate marker of bone strength in GIO patients treated with teriparatide. Introduction To investigate the correlations between biochemical markers of bone turnover and vertebral strength estimated by finite element analysis (FEA) in men with GIO. Methods A total of 92 men with GIO were included in an 18-month, randomized, open-label trial of teriparatide (20 μg/day, n = 45) and risedronate (35 mg/week, n = 47). High-resolution quantitative computed tomography images of the 12th thoracic vertebra obtained at baseline, 6 and 18 months were converted into digital nonlinear FE models and subjected to anterior bending, axial compression and torsion. Stiffness and strength were computed for each model and loading mode. Serum biochemical markers of bone formation (amino-terminal-propeptide of type I collagen [PINP]) and bone resorption (type I collagen cross-linked C-telopeptide degradation fragments [CTx]) were measured at baseline, 3 months, 6 months and 18 months. A mixed-model of repeated measures analysed changes from baseline and between-group differences. Spearman correlations assessed the relationship between changes from baseline of bone markers with FEA variables. Results PINP and CTx levels increased in the teriparatide group and decreased in the risedronate group. FEA-derived parameters increased in both groups, but were significantly higher at 18 months in the teriparatide group. Significant positive correlations were found between changes from baseline of PINP at 3, 6 and 18 months with changes in FE strength in the teriparatide-treated group, but not in the risedronate group. Conclusions Positive correlations between changes in a biochemical marker of bone formation and improvement of biomechanical properties support the use of PINP as a surrogate marker of bone strength in teriparatide-treated GIO patients.
    Full-text · Article · Jun 2013 · Osteoporosis International
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    ABSTRACT: Thesis (Ph. D.)--Stanford University, 1997. Submitted to the School of Education. Copyright by the author.
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