1. 3Biostatistics, Pacific University, Forest Grove, Oregon, USA
Clinical Utility of Biochemical Markers of Bone Turnover in Pediatric Patients with Osteopenia or Osteoporosis
Sasigarn A. Bowden, MD1, Chiazor Akusoba, Bsc2, John Hayes, PhD3, Ashley Bashioum, MD2, John D. Mahan, MD4
1Pediatric Endocrinology, 4Pediatric Nephrology, 2Nationwide Children’s Hospital/The Ohio State University, Columbus, Ohio, USA
3Biostatistics, Pacific University, Forest Grove, Oregon, USA
RESULTS
RESULTS
BACKGROUND
There were significant negative correlations between urine PD and both lumbar BMD (r=-0.48, p=0.001) and total BMC (r=-0.487, p=0.005) at baseline.
There were positive correlations between lumbar BMD and age ( r=0.6, p<0.001); between total BMC and age (r=0.374, p=0.006).
Serum osteocalcin and urine pyridinoline (PD) had significantly negative correlation with age (r=-0.282, p=0.032; r=-0.533, p<0.001).
There were no correlations between lumbar BMD Z score and any of the bone markers: urine PD, urine DPD, and serum osteocalcin.
There were significant positive correlations between serum osteocalcin and each of the following: serum alkaline phosphatase (r=0.31, p=0.015) [Figure 2], urine PD (r=0.321, p=0.026) [Figure 3], and urine DPD [Figure 4].
Serum osteocalcin, urine pyridinoline and urine deoxypyridinoline index, as expressed as a ratio of measured valued to upper limit of normal value for age, decreased during the first 3 years of bisphosphonates therapy.
The role of biochemical bone turnover markers in the care of pediatric patients with clinical bone fragility and/or low bone density is not well established.
It is unclear whether these markers are useful in assessing osteoporosis and monitoring the efficacy of antiresorptive therapy in pediatric patients.
Figure 5. There was a trend toward significant correlation between serum osteocalcin index and lumbar BMD Z score. Osteocalcin index was expressed as a ratio of measured osteocalcin and upper limit of normal value for age.
Figure 6. Bone markers index from baseline to years of bisphosphonate therapy. Index was expressed as a ratio of measured values and upper limit of normal range for age. Marker index decreased during the first 3 years of therapy.
OBJECTIVES
To examine the correlation of serum osteocalcin (OC) (bone formation marker) and urine pyridinoline (PD) and deoxypyridinoline (DPD) (bone resorption markers) with the bone mineral density (BMD), BMD Z scores, and other lab variables.
To evaluate the effects of bisphosphonate therapy on biochemical markers.
SUMMARY
Figure 1. Lumbar Z score increased significantly during the first 3 years of bisphosphonate therapy and then plateaued from year 4 to year 7.
Figure 2. Serum osteocalcin was positively correlated with serum alkaline phosphatase.
METHODS
There was a significant negative correlation between urine PD and lumbar BMD (r=-0.48, p=0.001), and total BMC (r=-0.487, p=0.005) at baseline.
There were positive correlations between lumbar BMD, total BMC with age (p<0.001).
Serum osteocalcin (OC) and urine PD had significantly negative correlations with age (p<0.05).
There was no correlation between urine PD, urine DPD, serum OC and lumbar BMD Z score.
There was a significant positive correlation between serum osteocalcin and urine pyridinoline, deoxypyridinoline and serum alkaline phosphatase, indicating higher level of serum osteocalcin with higher bone turnover.
Serum osteocalcin index had a weak association with lumbar BMD Z score.
We analyzed data obtained in 116 patients (mean age 9.9 years, 72 males) with clinical bone fragility and/or low BMD followed by the Metabolic Bone Clinic at Nationwide Children’s hospital from The study was approved by the Nationwide Children’s Hospital IRB.
Patients were classified as :
Osteogenesis imperfecta (41)
Immobilization from various neuromuscular disorders (57)
Juvenile osteoporosis (10)
Steroid-induced osteoporosis (7).
102 patients received bisphosphonates (95 pamidronate, 3 zoledronic acids, 2 risedronate, 2 alendronate).
Blood chemistries, PTH, serum osteocalcin (performed at Esoterix), urine pyridinoline and deoxypyridinoline (performed at Mayo Clinic) were obtained at baseline and yearly during and after the treatment.
Bone mineral content/density (BMC/BMD) was performed at baseline and yearly after bisphosphonates treatment, using Hologic dual-energy X-ray absorptiometry (DEXA; Hologic Delphi, Waltham, MA).
The Z score of the lumbar spine BMD was determined using locally derived normative data adjusted for body weight and Tanner staging1.
Pearson’s correlation and regression were performed to assess the relationship between bone markers and different bone parameters, using SPSS 14.0 (SPSS, Chicago, IL)
CONCLUSIONS
Figure 4. Serum osteocalcin was positively correlated with urine deoxypyridinoline.
Figure 3. Serum osteocalcin was positively correlated with urine pyridinoline.
In children with clinical bone fragility and/or low bone density, biochemical bone turnover markers were correlated with BMD, tBMC but not weight/Tanner corrected lumbar BMD Z score.
While the bone turnover markers were not reliable predictors of degree of low bone density, the bone markers showed suppression during bisphosphonate therapy and may be helpful in monitoring the response to therapy.
REFERENCES
1.Southard RN, Morris JD, Mahan JD, Hayes JR, Torch MA, Sommer A, Zipf WB. Bone mass in healthy children: measurement with quantitative DXA. Radiology. 1991June; 79(3);735-8.