A Subtrochanteric Femoral Stress Fracture following Bisphosphonate Treatment in an Adolescent Girl

Abstract

Atypical subtrochanteric and diaphyseal femoral fractures (AFFs) have emerged as a potential complication of bisphosphonate treatment in adults. Despite increasing off-label use of bisphosphonates in children and adolescents for a variety of skeletal disorders, there have been no reports of AFFs in children or adolescents outside of the osteogenesis imperfecta population. We present the case of a 16-year-old girl who developed a subtrochanteric femoral stress fracture following pamidronate treatment for idiopathic juvenile osteoporosis.

Osteonecrosis of the Jaw and Rebound Hypercalcemia in Young People Treated With Denosumab for Giant Cell Tumor of Bone

“…Bisphosphonates have also been associated with suspected atypical femoral fractures in children (10,11) although not confirmed in larger series (20,21). Several studies have assessed the risk of developing ONJ in bisphosphonate-treated children following dental treatment (22,23), however no cases have been reported so far.…”

“…In children and adolescents with osteogenesis imperfecta and osteoporosis, prolonged or high dose bisphosphonate therapy has been associated with iatrogenic osteopetrosis (9) and suspected atypical femoral fractures (10,11), but never with ONJ (12) or rebound hypercalcaemia. To date, safety data for denosumab in adolescents are sparse since only 3.5% (n=10 of 282) of patients in the GCTB safety trial were adolescents (aged 13-17 years) (3).…”

Bisphosphonate Withdrawal: Effects on Bone Formation and Bone Resorption in Maturing Male Mice

“…(18) However, 2 years after stopping bisphosphonates, an increase in bone mineral density and bone mineral content associated with increased bone resorption markers is observed in children. (9) Recent case reports (21)(22)(23)(24) of atypical femoral fractures in pediatric patients receiving long-term bisphosphonate therapy highlight the risks of chronic bisphosphonate therapy in growing children. The preclinical data presented in the current studies suggest that intermittent "drug holidays" may present an opportunity for resumption of bone formation in the setting of continued suppression of bone resorption, thereby enhancing the increase in bone found with bisphosphonates while minimizing the long-term risks of chronic bisphosphonate therapy on the growing skeleton.…”

Consensus guidelines on the use of bisphosphonate therapy in children and adolescents

“…88 There are very few reports of similar lesions in the paediatric skeleton. 89,90 Two recent reviews of cohorts of young people with OI call into question the possibility of 'atypical' femoral fractures. 91,92 Bisphosphonate-induced osteonecrosis of the jaw Recommendation Dental review should be undertaken prior to the first dose of bisphosphonate, with any invasive dental work completed before a first dose.…”