Medical Professional Publications

Bone Turnover Markers Can Help Monitor Response in Children With Bone Fragility Treated With Bone-Strengthening Therapy

Columbus, OH — January 2017

A number of studies have shown that in adults, bone turnover markers can be used to predict changes in bone mineral density — and to track the effectiveness of (and patients’ compliance with) bisphosphonate treatments. Bone metabolism in growing children is more complex, though, and there is little research demonstrating the utility of turnover markers in analyzing children with clinical bone fragility.  

A recent study led by physician-researchers at Nationwide Children’s Hospital has begun to remedy that. The paper, published in the Journal of Pediatric Endocrinology and Metabolism, found that bone turnover markers can be used to monitor treatment effectiveness in these pediatric patients. Those same markers, however, are not dependable predictors of degree of low bone mineral density.

“Bone turnover marker assays are readily available, and now we have some evidence of their usefulness as metrics for monitoring therapy in children with poor bone health,” says Sasigarn Bowden, MD, a pediatric endocrinologist at Nationwide Children’s, member of the physician team at the hospital’s Metabolic Bone Clinic and lead author of the study.

The study examined 115 patients (mean age 9.7 years) with clinical bone fragility; 41 were diagnosed with osteogenesis imperfecta, 10 with juvenile osteoporosis, seven with steroid-induced osteoporosis and 57 were immobilized as a result of neuromuscular disorders.  All but 13 patients were treated with bisphosphonates.

The authors measured two bone formation-specific markers, alkaline phosphatase (ALP) and osteocalcin (OC), as well as two bone-resorption specific markers, urine pyridinoline (PD) and deoxypyridinoline (DPD). Those markers, along with bone mineral density, were noted at baseline and in yearly follow-ups (mean duration of follow-up was eight years). Reference values for bone turnover markers can vary in different age groups in the pediatric population, so the authors calculated “indexes,” or ratios of measured values to the upper limit of normal values for age, for OC, PD and DPC.

Among the findings:

  • There were significant correlations between serum OC and ALP, PD and DPD. Those are also seen in healthy children, suggesting the same bone turnover processes occur in children with and without bone disease.
  • OC, PD and DPD indexes tended to decrease while bone density increases during the first three years of bisphosphonate therapy, indicating suppressed bone turnover during the anti-resorptive therapy.
  • There were no significant correlations between degree of low bone mineral density (lumbar bone mineral density Z-score) and values of any bone turnover marker, but there was a trend toward significance between serum OC index and lumbar BMD Z-score.

“We can and do use these bone turnover markers to monitor treatment,” says Dr. Bowden, who is also an associate professor of Clinical Pediatrics at The Ohio State College of Medicine. “If a patient is taking oral alendronate, we can monitor that patient’s compliance. We still do not know, however, if these markers can help us track some clinical responses in shorter intervals long before improvement in bone mineral density can be seen, or if they can be helpful in predicting fracture risk reduction after therapy. We need additional studies to determine if bone turnover markers can also be useful in guiding treatment plans, in terms of the optimal bisphosphonate dose or length of therapy.”

Citation:
Bowden SA, Akusoba CI, Hayes JR, Mahan JD. Biochemical markers of bone turnover in children with clinical bone fragility. Journal of Pediatric Endocrinology and Metabolism. 2016 Jun 1;29(6):715-22.

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