Effects of IV bisphosphonates last 2-3 years in children

CHICAGO – Serum osteocalcin is the first bone turnover marker to recover after intravenous bisphosphonate therapy in children with primary osteoporosis, secondary osteoporosis, or osteogenesis imperfecta, making it a good indicator that it’s time to consider a second round of treatment, according to investigators from Children’s Mercy Hospitals and Clinics in Kansas City, Mo.

In a review of 104 children followed for up to 5 years, they found that the benefits of IV bisphosphonates – for children, usually two or three 2-day courses about 4 months apart – remain durable for up to 3 years. After an initial decrease, serum osteocalcin starts to return to baseline 1 year after the start of treatment (P = 0.007); improvements in lumbar spine bone mineral density z scores on dual energy x-ray absorptiometry (DXA) start to plateau at about 2 years and then reverse after 3 years (P less than 0.0001). Decreases in urine N-telopeptide, a bone resorption marker, plateau at 2-3 years, then start to increase after 3 years (P less than 0.0001). Serum bone-specific alkaline phosphatase, a marker of bone formation like osteocalcin, continues to decrease for about 4.8-5 years (P less than 0.0001).

Although alkaline phosphatase, urine N-telopeptide, and lumbar z scores had begun to recover by the end of follow-up, they were still significantly improved over baseline. For instance, baseline lumbar z scores, more than two standard deviations below normal before treatment, were 1.31 standard deviations below normal at last follow up (P = 0.002).

However, after initial improvement, there was no statistically significant change in serum osteocalcin from baseline; the mean baseline value was 52.7 ng/mL, and mean value at last follow up was 54.5 ng/mL (P = 0.48).

"Osteocalcin is the first marker to increase within the first year after start of bisphosphonate therapy. The results of the study," perhaps the first to define the drug holiday window for bisphosphonates in children, "provide a framework [for] when to anticipate reinitiation of bisphosphonate therapy," the investigators concluded at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.

"After 3 years, we should consider reinitiation of bisphosphonates in these children," said lead investigator Dr. Naziya Tahseen of the department of pediatric endocrinology at Children’s Mercy Hospitals and Clinics.

The subjects’ mean age was 11.6 years, 61 (58.7%) were girls, 67 (64.4%) were in puberty, and 75 (72.1%) were ambulatory; 59 (56.7%) children had primary or secondary osteoporosis, 26 (25%) had osteopenia, and 19 (18.3%) osteogenesis imperfecta. Lab values were followed every 4 months, with DXA scans repeated every 6-12 months.

Overall, children did better if they were ambulatory, but puberty status and gender had no effect.

The investigators had no relevant disclosures, and no outside funding was used for the project.

[email protected]

CHICAGO – Serum osteocalcin is the first bone turnover marker to recover after intravenous bisphosphonate therapy in children with primary osteoporosis, secondary osteoporosis, or osteogenesis imperfecta, making it a good indicator that it’s time to consider a second round of treatment, according to investigators from Children’s Mercy Hospitals and Clinics in Kansas City, Mo.

In a review of 104 children followed for up to 5 years, they found that the benefits of IV bisphosphonates – for children, usually two or three 2-day courses about 4 months apart – remain durable for up to 3 years. After an initial decrease, serum osteocalcin starts to return to baseline 1 year after the start of treatment (P = 0.007); improvements in lumbar spine bone mineral density z scores on dual energy x-ray absorptiometry (DXA) start to plateau at about 2 years and then reverse after 3 years (P less than 0.0001). Decreases in urine N-telopeptide, a bone resorption marker, plateau at 2-3 years, then start to increase after 3 years (P less than 0.0001). Serum bone-specific alkaline phosphatase, a marker of bone formation like osteocalcin, continues to decrease for about 4.8-5 years (P less than 0.0001).

Although alkaline phosphatase, urine N-telopeptide, and lumbar z scores had begun to recover by the end of follow-up, they were still significantly improved over baseline. For instance, baseline lumbar z scores, more than two standard deviations below normal before treatment, were 1.31 standard deviations below normal at last follow up (P = 0.002).

However, after initial improvement, there was no statistically significant change in serum osteocalcin from baseline; the mean baseline value was 52.7 ng/mL, and mean value at last follow up was 54.5 ng/mL (P = 0.48).

"Osteocalcin is the first marker to increase within the first year after start of bisphosphonate therapy. The results of the study," perhaps the first to define the drug holiday window for bisphosphonates in children, "provide a framework [for] when to anticipate reinitiation of bisphosphonate therapy," the investigators concluded at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.

"After 3 years, we should consider reinitiation of bisphosphonates in these children," said lead investigator Dr. Naziya Tahseen of the department of pediatric endocrinology at Children’s Mercy Hospitals and Clinics.

The subjects’ mean age was 11.6 years, 61 (58.7%) were girls, 67 (64.4%) were in puberty, and 75 (72.1%) were ambulatory; 59 (56.7%) children had primary or secondary osteoporosis, 26 (25%) had osteopenia, and 19 (18.3%) osteogenesis imperfecta. Lab values were followed every 4 months, with DXA scans repeated every 6-12 months.

Overall, children did better if they were ambulatory, but puberty status and gender had no effect.

The investigators had no relevant disclosures, and no outside funding was used for the project.

[email protected]

CHICAGO – Serum osteocalcin is the first bone turnover marker to recover after intravenous bisphosphonate therapy in children with primary osteoporosis, secondary osteoporosis, or osteogenesis imperfecta, making it a good indicator that it’s time to consider a second round of treatment, according to investigators from Children’s Mercy Hospitals and Clinics in Kansas City, Mo.

In a review of 104 children followed for up to 5 years, they found that the benefits of IV bisphosphonates – for children, usually two or three 2-day courses about 4 months apart – remain durable for up to 3 years. After an initial decrease, serum osteocalcin starts to return to baseline 1 year after the start of treatment (P = 0.007); improvements in lumbar spine bone mineral density z scores on dual energy x-ray absorptiometry (DXA) start to plateau at about 2 years and then reverse after 3 years (P less than 0.0001). Decreases in urine N-telopeptide, a bone resorption marker, plateau at 2-3 years, then start to increase after 3 years (P less than 0.0001). Serum bone-specific alkaline phosphatase, a marker of bone formation like osteocalcin, continues to decrease for about 4.8-5 years (P less than 0.0001).

Although alkaline phosphatase, urine N-telopeptide, and lumbar z scores had begun to recover by the end of follow-up, they were still significantly improved over baseline. For instance, baseline lumbar z scores, more than two standard deviations below normal before treatment, were 1.31 standard deviations below normal at last follow up (P = 0.002).

However, after initial improvement, there was no statistically significant change in serum osteocalcin from baseline; the mean baseline value was 52.7 ng/mL, and mean value at last follow up was 54.5 ng/mL (P = 0.48).

"Osteocalcin is the first marker to increase within the first year after start of bisphosphonate therapy. The results of the study," perhaps the first to define the drug holiday window for bisphosphonates in children, "provide a framework [for] when to anticipate reinitiation of bisphosphonate therapy," the investigators concluded at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.

"After 3 years, we should consider reinitiation of bisphosphonates in these children," said lead investigator Dr. Naziya Tahseen of the department of pediatric endocrinology at Children’s Mercy Hospitals and Clinics.

The subjects’ mean age was 11.6 years, 61 (58.7%) were girls, 67 (64.4%) were in puberty, and 75 (72.1%) were ambulatory; 59 (56.7%) children had primary or secondary osteoporosis, 26 (25%) had osteopenia, and 19 (18.3%) osteogenesis imperfecta. Lab values were followed every 4 months, with DXA scans repeated every 6-12 months.

Overall, children did better if they were ambulatory, but puberty status and gender had no effect.

The investigators had no relevant disclosures, and no outside funding was used for the project.

[email protected]