Do femoral fractures in adult patients with osteogenesis imperfecta imitate atypical femoral fractures? A case series.

Atypical femoral fractures (AFFs) are low-energy femoral fractures with characteristic radiological features and a suspected relation to treatment with bisphosphonate (BP) or denosumab. In osteogenesis imperfecta (OI), BP is currently the drug of choice when medical treatment is indicated. Due to bone deformities, the radiologic appearance of femoral fractures may be different in patients with OI and patients with osteoporosis. We investigated the prevalence and appearance of femoral fractures in a cohort of adult patients with confirmed OI (55 patients, age range 19-69 years, 26 women (47%) and 35 patients (64%) had received BP treatment), who attended the outpatient clinic at Aarhus University Hospital. The fractures were evaluated according to major and minor AFF criteria. In our OI cohort, we found that eight out of 55 patients had suffered a femoral fracture in adult year: five women and three men, aged 25 to 54 years. One patient had OI type I, two had OI type III, four had OI type IV, and one had OI type V. All fractures were associated with no or minimal trauma. Four patients had fractures that fulfilled the criteria of AFFs. Two of the four patients had received long-term BP treatment prior to the fracture and three patients had severe deformities of the femur. Femoral fractures in OI imitate AFFs. This suggests that bone deformity, collagen deficiencies, and alterations in mineralization of bone may cause femoral fractures that imitate AFFs even in the absence of antiresorptive treatment. Bone deformities should be monitored as part of the management of adult patients with OI. Continuous dull or aching pain in the groin or thigh should lead to radiographic examination. The radiologic appearance of femoral fractures may be different in patients with osteogenesis imperfecta (OI) and patients with osteoporosis, thus imitate atypical femoral fractures (AFF). We found that bone deformity, collagen deficiencies, and alterations in bone mineralization may cause femoral fractures that imitate AFFs even in the absence of antiresorptive treatment.

Bone nanostructure near titanium and porous tantalum implants studied by scanning small angle x-ray scattering.

Bone sections including either titanium or porous tantalum implant devices used for interbody spinal fusion were investigated with position-resolved small angle X-ray scattering (sSAXS). The samples were obtained from six-month-old pigs that had undergone surgery three months prior to sacrifice. The aim of the study was to explore the possibility of using sSAXS to obtain information about thickness, orientation and shape/arrangement of the mineral crystals in bone near the implant surfaces. Detailed sSAXS scans were carried out in two different regions of bone adjacent to the implant in each of the implant samples. In the implant vicinity the mineral crystals tended to be aligned with the surface of the implants. The mean crystal thickness was between 2.1 and 3.0 nm. The mineral crystal thickness increased linearly with distance from the implant in both regions of the porous tantalum implant and in one of the regions in the titanium sample. In the second region of the titanium sample the thickest mineral crystals were found close to the implant surface. The observed differences in mineral thickness with distance from the implant surfaces might be explained by differences in mechanical load induced by the implant material and the geometrical design of the implant. The study shows that sSAXS is a powerful tool to characterize the nanostructure of bone near implant surfaces.

Semiquantitative mRNA measurements of osteoinductive growth factors in human iliac-crest bone: expression of LMP splice variants in human bone.

Although osteotropic growth factors are known to play an important role in bone metabolism, knowledge about their expression in relation to age, sex and smoking remains limited. In this study we report mRNA levels of the recently discovered Lim mineralization protein splice variants (LMP-1, LMP-2, LMP-3) and the established osteotropic growth factors BMP-2, BMP-6, BMP-7, TGF-beta, IGF-I, IGF-II and b-FGF in human iliac crest bone. Standardized bone biopsy specimens were obtained from the iliac crest during graft harvesting in 62 patients (38 males, 24 females, mean age 44.7 years, range 13-78 years) undergoing spinal surgery. Samples were immediately stored in liquid nitrogen for PCR analysis. Semi-quantitative RT-PCR was performed for TGF-beta, IGF-I, IGF-II, BMP2, BMP-6, BMP7, bFGF, LMP-1, LMP-2 and LMP-3 using beta-actin as internal standard. Triplicate measurements were made of each growth factor and beta-actin. mRNA for all examined growth factors was detected in 69% of the specimens. The lowest degree of detection was present for b-FGF and BMP-2, both of which were found in 85% of the specimens. LMP-1 was detected in 98% of the specimens. LMP-2 in 94% and LMP-3 in 27%, respectively. LMP-1 was generally expressed in higher amounts than LMP-2 and LMP-3. Nondetectable levels of the growth factors were more frequent in the >60-year-old males compared with >60-year-old females ( P < 0.05) and <60-year-old males ( P < 0.01). LMP-1 expression was more variable among young individuals, but mean values were similar between age groups. TGF-beta, BMP-2 and BMP-7 values did not differ between age groups, but generally a higher variation was found among older patients. IGF-I values were significantly higher ( P < 0.05) in males over 60 years, whereas the highest level of bFGF mRNA was present in males younger than 20 years ( P < 0.05). In addition, regression analysis revealed correlation between BMP-2 and BMP-7 (R2 = 0.74, P < 0.0005), LMP-2 and BMP-2 (R2 = 0.27, P < 0.0005) and LMP-2 and bFGF (R2 = 0.40, P < 0.0005). In conclusion, we have demonstrated expression of LMP-1 and LMP-2 in human bone. LMP-1 was expressed in higher amounts and showed a higher degree of variation among young individuals. LMP-2 was correlated to a number of other growth factors, suggesting that LMPs may also play a role in human bone metabolism. Higher variation in the expression of TGF-beta, BMP-2 and BMP-7 was found in the older age groups, but whether or not this can be correlated to age-related changes in bone turnover requires further studies.