AACE: Bisphosphonates do not prevent fractures in adults with osteogenesis imperfecta

NASHVILLE, TENN. – Bisphosphonates help prevent fractures in some children with osteogenesis imperfecta, but they don't do the same for adults with the condition, according to a review from Johns Hopkins University and the Kennedy Krieger Institute.

Even so, bisphosphonates are used widely for adult osteogenesis imperfecta (OI) “because people have nothing else to hang their hat on, and the average physician doesn’t understand that osteogenesis imperfecta is not the same as age-related osteoporosis,” said senior investigator Dr. Jay R. Shapiro, director of Kennedy Krieger’s osteogenesis imperfecta program in Baltimore.

“We see adults with OI all the time who have been on bisphosphonates for 10 years, 12 years. It’s not doing anything for them, and sooner or later they come to realize that.” Meanwhile, “I think people are getting a little bit of a queasy feeling about not fully understanding the effectiveness and side effects of long-term treatment with bisphosphonates,” said Dr. Shapiro, also professor in the department of physical medicine and rehabilitation at Johns Hopkins University, Baltimore.

Adults with OI “also don’t respond to Forteo [teriparatide]. I do not recommend treatment with bisphosphonates or Forteo in” adults, he said at the annual meeting of the American Association of Clinical Endocrinologists.

Dr. Shapiro shared his thoughts during an interview regarding his latest study, an analysis of five children with OI under 18 years of age who responded to pamidronate (Aredia) and 11 who did not, meaning that they had two or more fractures per year while on the drug.

His team also compared fracture outcomes in 34 adults with OI treated with oral or intravenous bisphosphonates with 12 untreated adults. The adults were, on average, 52 years old.

The goal was to see if common bone markers predicted who would respond to bisphosphonates, but they did not. Vitamin D, phosphorus, alkaline phosphatase, C-telopeptide, and other measures were the same in children regardless of their response to pamidronate, and the same in adults with OI whether or not they were on bisphosphonates.

“We have not yet defined what the difference is between responders and nonresponders. If you take a crack at the simple things, they don’t help,” Dr. Shapiro said.

Children who responded had a mean of 4.8 fractures over an average of 42.6 months of treatment. Nonresponders had a mean of 15.6 fractures over an average of 72.7 months of treatment.

“For a period of time, you can expect about two-thirds of kids to respond. I would look to see a decrease in fracture rates within 2 years of treatment. If they haven’t decreased their fracture rate [by then], I would be very cautious about continuing,” he said, adding that the optimal duration of treatment in children is unknown.

In adults, the team found no difference in fracture rates at 5 and 10 years. Treated adults had an average of 1.71 fractures over 10 years, versus 1.23 in untreated adults (P = 0.109).

The numbers in the study were too small for meaningful subgroup analysis by OI type.

The findings parallel recent meta-analyses; some have found that bisphosphonates help OI children, but none has found benefits for adults (J. Bone. Miner. Res. 2015;30:929-33). “To date, there is no evidence indicating that bisphosphonates have a positive effect on fracture rates in adults,” Dr. Shapiro said.

Bone turnover declines after puberty, which may explain why the drugs lose their effectiveness after age 18 or so. “What happens in OI anyway is that, after puberty, the fracture rates normally go way down,” Dr. Shapiro said.

Dr. Shapiro said that he had no relevant disclosures, and that there was no outside funding for the work.

[email protected]

NASHVILLE, TENN. – Bisphosphonates help prevent fractures in some children with osteogenesis imperfecta, but they don't do the same for adults with the condition, according to a review from Johns Hopkins University and the Kennedy Krieger Institute.

Even so, bisphosphonates are used widely for adult osteogenesis imperfecta (OI) “because people have nothing else to hang their hat on, and the average physician doesn’t understand that osteogenesis imperfecta is not the same as age-related osteoporosis,” said senior investigator Dr. Jay R. Shapiro, director of Kennedy Krieger’s osteogenesis imperfecta program in Baltimore.

“We see adults with OI all the time who have been on bisphosphonates for 10 years, 12 years. It’s not doing anything for them, and sooner or later they come to realize that.” Meanwhile, “I think people are getting a little bit of a queasy feeling about not fully understanding the effectiveness and side effects of long-term treatment with bisphosphonates,” said Dr. Shapiro, also professor in the department of physical medicine and rehabilitation at Johns Hopkins University, Baltimore.

Adults with OI “also don’t respond to Forteo [teriparatide]. I do not recommend treatment with bisphosphonates or Forteo in” adults, he said at the annual meeting of the American Association of Clinical Endocrinologists.

Dr. Shapiro shared his thoughts during an interview regarding his latest study, an analysis of five children with OI under 18 years of age who responded to pamidronate (Aredia) and 11 who did not, meaning that they had two or more fractures per year while on the drug.

His team also compared fracture outcomes in 34 adults with OI treated with oral or intravenous bisphosphonates with 12 untreated adults. The adults were, on average, 52 years old.

The goal was to see if common bone markers predicted who would respond to bisphosphonates, but they did not. Vitamin D, phosphorus, alkaline phosphatase, C-telopeptide, and other measures were the same in children regardless of their response to pamidronate, and the same in adults with OI whether or not they were on bisphosphonates.

“We have not yet defined what the difference is between responders and nonresponders. If you take a crack at the simple things, they don’t help,” Dr. Shapiro said.

Children who responded had a mean of 4.8 fractures over an average of 42.6 months of treatment. Nonresponders had a mean of 15.6 fractures over an average of 72.7 months of treatment.

“For a period of time, you can expect about two-thirds of kids to respond. I would look to see a decrease in fracture rates within 2 years of treatment. If they haven’t decreased their fracture rate [by then], I would be very cautious about continuing,” he said, adding that the optimal duration of treatment in children is unknown.

In adults, the team found no difference in fracture rates at 5 and 10 years. Treated adults had an average of 1.71 fractures over 10 years, versus 1.23 in untreated adults (P = 0.109).

The numbers in the study were too small for meaningful subgroup analysis by OI type.

The findings parallel recent meta-analyses; some have found that bisphosphonates help OI children, but none has found benefits for adults (J. Bone. Miner. Res. 2015;30:929-33). “To date, there is no evidence indicating that bisphosphonates have a positive effect on fracture rates in adults,” Dr. Shapiro said.

Bone turnover declines after puberty, which may explain why the drugs lose their effectiveness after age 18 or so. “What happens in OI anyway is that, after puberty, the fracture rates normally go way down,” Dr. Shapiro said.

Dr. Shapiro said that he had no relevant disclosures, and that there was no outside funding for the work.

[email protected]

NASHVILLE, TENN. – Bisphosphonates help prevent fractures in some children with osteogenesis imperfecta, but they don't do the same for adults with the condition, according to a review from Johns Hopkins University and the Kennedy Krieger Institute.

Even so, bisphosphonates are used widely for adult osteogenesis imperfecta (OI) “because people have nothing else to hang their hat on, and the average physician doesn’t understand that osteogenesis imperfecta is not the same as age-related osteoporosis,” said senior investigator Dr. Jay R. Shapiro, director of Kennedy Krieger’s osteogenesis imperfecta program in Baltimore.

“We see adults with OI all the time who have been on bisphosphonates for 10 years, 12 years. It’s not doing anything for them, and sooner or later they come to realize that.” Meanwhile, “I think people are getting a little bit of a queasy feeling about not fully understanding the effectiveness and side effects of long-term treatment with bisphosphonates,” said Dr. Shapiro, also professor in the department of physical medicine and rehabilitation at Johns Hopkins University, Baltimore.

Adults with OI “also don’t respond to Forteo [teriparatide]. I do not recommend treatment with bisphosphonates or Forteo in” adults, he said at the annual meeting of the American Association of Clinical Endocrinologists.

Dr. Shapiro shared his thoughts during an interview regarding his latest study, an analysis of five children with OI under 18 years of age who responded to pamidronate (Aredia) and 11 who did not, meaning that they had two or more fractures per year while on the drug.

His team also compared fracture outcomes in 34 adults with OI treated with oral or intravenous bisphosphonates with 12 untreated adults. The adults were, on average, 52 years old.

The goal was to see if common bone markers predicted who would respond to bisphosphonates, but they did not. Vitamin D, phosphorus, alkaline phosphatase, C-telopeptide, and other measures were the same in children regardless of their response to pamidronate, and the same in adults with OI whether or not they were on bisphosphonates.

“We have not yet defined what the difference is between responders and nonresponders. If you take a crack at the simple things, they don’t help,” Dr. Shapiro said.

Children who responded had a mean of 4.8 fractures over an average of 42.6 months of treatment. Nonresponders had a mean of 15.6 fractures over an average of 72.7 months of treatment.

“For a period of time, you can expect about two-thirds of kids to respond. I would look to see a decrease in fracture rates within 2 years of treatment. If they haven’t decreased their fracture rate [by then], I would be very cautious about continuing,” he said, adding that the optimal duration of treatment in children is unknown.

In adults, the team found no difference in fracture rates at 5 and 10 years. Treated adults had an average of 1.71 fractures over 10 years, versus 1.23 in untreated adults (P = 0.109).

The numbers in the study were too small for meaningful subgroup analysis by OI type.

The findings parallel recent meta-analyses; some have found that bisphosphonates help OI children, but none has found benefits for adults (J. Bone. Miner. Res. 2015;30:929-33). “To date, there is no evidence indicating that bisphosphonates have a positive effect on fracture rates in adults,” Dr. Shapiro said.

Bone turnover declines after puberty, which may explain why the drugs lose their effectiveness after age 18 or so. “What happens in OI anyway is that, after puberty, the fracture rates normally go way down,” Dr. Shapiro said.

Dr. Shapiro said that he had no relevant disclosures, and that there was no outside funding for the work.

[email protected]