Abstract

A drawback in the use of bone mineral density (BMD) measurements to monitor the effect of antiresorptive treatment is that 1 or 2 years of successful treatment may be necessary before significant increases in BMD can be detected (1). Biochemical markers can enable dynamic and rapid measurement of total body skeletal metabolism and may be clinically useful, particularly for detecting the effects of osteoporosis therapy (2). Circulating osteocalcin (OC), a bone-specific protein produced by osteoblasts, is widely used as an index of bone formation (3)(4). Fragments of OC are also found in urine (5)(6)(7), and the measurement of urinary OC (U-OC) is another method for monitoring bone metabolism (8)(9)(10)(11). We recently described 3 immunoassays for measuring U-OC (11). Here we report the use of U-OC assays to monitor the effect of alendronate, a bisphosphonate and bone resorption inhibitor widely used to treat osteoporosis (12). The study included 164 healthy women, postmenopausal for 1–5 years [mean (SD) age, 53.1 (2.3) years], described in detail previously (13). The study was a 1-year, double-blind, randomized, placebo-controlled intervention trial with 2 experimental groups: one receiving alendronate (5 mg/day Fosamax; Merck & Co) and the other receiving placebo (donated by Merck & Co). All participants in both study groups received a daily supplement of calcium carbonate (630 mg) and vitamin D3 (200 IU = 5 μg; Citracal + D; Mission Pharmacal). We collected 24-h urine samples and serum samples after a 12-h fast at baseline and after 3, 6, and 12 months. The samples were stored at −70 °C. U-OC was measured with U-MidOC, U-LongOC, and U-TotalOC assays, which all have unique specificities toward different naturally occurring U-OC fragments (11). Results were normalized for urinary creatinine determined in accordance with the …

Highlights

  • A drawback in the use of bone mineral density (BMD) measurements to monitor the effect of antiresorptive treatment is that 1 or 2 years of successful treatment may be necessary before significant increases in BMD can be detected (1 )

  • Fragments of OC are found in urine (5–7 ), and the measurement of urinary OC (U-OC) is another method for monitoring bone metabolism (8 –11 )

  • We report the use of U-OC assays to monitor the effect of alendronate, a bisphosphonate and bone resorption inhibitor widely used to treat osteoporosis (12 )

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Summary

Introduction

A drawback in the use of bone mineral density (BMD) measurements to monitor the effect of antiresorptive treatment is that 1 or 2 years of successful treatment may be necessary before significant increases in BMD can be detected (1 ). After 3 months, U-MidOC, U-LongOC, and U-TotalOC values decreased to 41.5 (32.4 –59.3)%, 33.7 (25.8 –53.0)%, and 59.2 (41.7– 81.5)% of baseline, respectively (Fig. 1, A–C). The concentrations relative to baseline after 3 months were as follows: U-MidOC, 75.4 (61.0 – 89.2)%; U-LongOC, 70.3 (51.3–91.7)%; U-TotalOC, 98.5 (79.3– 133.0)%; and S-TotalOC, 88.4 (79.2–105.6)% (Fig. 1, A–D).

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