Differences in femur geometry and bone markers in atypical femur fractures and the general population

Bisphosphonate (BP) therapy for moderate to severe osteogenesis imperfecta (OI) has become a mainstay of treatment in the last three decades. Given the significant improvements in bone mineral density and theoretical reductions in fracture risk, many patients are treated with bisphosphonates for prolonged periods of time. There currently lacks consensus in the optimal duration of BP therapy for patients with OI, and patients are often treated on a case-by-case basis. Long-term BP therapy has been associated with atypical femur fractures in adult patients treated for osteoporosis. The American Society for Bone and Mineral Research concluded that the median duration of BP therapy in patients with atypical femur fractures was 7 years. The role of long-term BP therapy in OI patients with atypical femur fractures remains unclear. Here, a case report is presented of an adolescent patient with type V OI that sustained a subtrochanteric femur fracture with features of an atypical pattern following treatment with intravenous pamidronate for 10.5 years. At the time of injury, the contralateral femur was also found to have atypical features suggestive of an impending fracture. The completed fracture was treated with closed reduction and cephalomedullary nail fixation. The impending fracture was prophylactically stabilized using the same technique. Prior to the injury, limb-length radiographs obtained to evaluate lower extremity alignment demonstrated features of an impending fracture but went unnoticed. Further studies are needed to clarify the role of long-term BP therapy in patients with OI suffering from atypical femur fractures.

Background:Dual energy X-ray absoprtiometry is the reference method to mesure bone mineral density (1). Loss of bone mineral density is significant if it exceeds the least significant change. The threshold value used in general population is 0,03 g/cm2 (2). Patients with obesity are known for having a higher bone mineral density due to metabolism and physiopathology characteristics (3,4).Objectives:The aim of our study was to determine the least significant change in bone densitometry in patients with obesity.Methods:We conducted an interventionnal study in 120 patients with obesity who performed a bone densitometry. We measured twice the bone mineral density at the lumbar spine, the femoral neck and the total hip in the same time (5,6). We determined the least significant change in bone densitometry from each pair of measurements, using the Bland and Altman method. We also determined the least significant change in bone densitometry according to each stage of obesity.Results:The least significant change in bone densitometry in patients with obesity is 0,046g/cm2 at the lumbar spine, 0.069 g/cm2 at the femoral neck and 0.06 g/cm2 at the total hip.Conclusion:The least significant change in bone densitometry in patients with obesity is higher than in general population. These results may improve DXA interpretation in this specific population, and may personnalize their medical care.References:[1]Lees B, Stevenson JC. An evaluation of dual-energy X-ray absorptiometry and comparison with dual-photon absorptiometry. Osteoporos Int. mai 1992;2(3):146-52.[2]Briot K, Roux C, Thomas T, Blain H, Buchon D, Chapurlat R, et al. Actualisation 2018 des recommandations françaises du traitement de l’ostéoporose post-ménopausique. Rev Rhum. oct 2018;85(5):428-40.[3]Shapses SA, Pop LC, Wang Y. Obesity is a concern for bone health with aging. Nutr Res N Y N. mars 2017;39:1-13.[4]Savvidis C, Tournis S, Dede AD. Obesity and bone metabolism. Hormones. juin 2018;17(2):205-17.[5]Roux C, Garnero P, Thomas T, Sabatier J-P, Orcel P, Audran M, et al. Recommendations for monitoring antiresorptive therapies in postmenopausal osteoporosis. Jt Bone Spine Rev Rhum. janv 2005;72(1):26-31.[6]Ravaud P, Reny JL, Giraudeau B, Porcher R, Dougados M, Roux C. Individual smallest detectable difference in bone mineral density measurements. J Bone Miner Res. août 1999;14(8):1449-56.Disclosure of Interests:None declared.

In patients with phenylketonuria (PKU), treated by diet therapy only, evidence suggests that areal bone mineral density (BMDa) is within the normal clinical reference range but is below the population norm. Aims: To study longitudinal bone density, mass, and geometry over 36 months in children with PKU taking either amino acid (L-AA) or casein glycomacropeptide substitutes (CGMP-AA) as their main protein source. Methodology: A total of 48 subjects completed the study, 19 subjects in the L-AA group (median age 11.1, range 5–6 years) and 29 subjects in the CGMP-AA group (median age 8.3, range 5–16years). The CGMP-AA was further divided into two groups, CGMP100 (median age 9.2, range 5–16years) (n = 13), children taking CGMP-AA only and CGMP50 (median age 7.3, range 5–15years) (n = 16), children taking a combination of CGMP-AA and L-AA. Dual X-ray absorptiometry (DXA) was measured at enrolment and 36 months, peripheral quantitative computer tomography (pQCT) at 36 months only, and serum blood and urine bone turnover markers (BTM) and blood bone biochemistry at enrolment, 6, 12, and 36 months. Results: No statistically significant differences were found between the three groups for DXA outcome parameters, i.e., BMDa (L2–L4 BMDa g/cm2), bone mineral apparent density (L2–L4 BMAD g/cm3) and total body less head BMDa (TBLH g/cm2). All blood biochemistry markers were within the reference ranges, and BTM showed active bone turnover with a trend for BTM to decrease with increasing age. Conclusions: Bone density was clinically normal, although the median z scores were below the population mean. BTM showed active bone turnover and blood biochemistry was within the reference ranges. There appeared to be no advantage to bone density, mass, or geometry from taking a macropeptide-based protein substitute as compared with L-AAs.