Enrique Caceres

Polymorphisms in the interleukin-6 receptor gene are associated with bone mineral density and body mass index in Spanish postmenopausal women

OBJECTIVE Osteoporosis and obesity are complex diseases with a strong genetic component. Bone mineral density (BMD) and body mass index (BMI) linkage studies identified a locus at 1q21-23, where the interleukin-6 receptor (IL6R) gene is located. The IL6R and the gp130 receptors are the mediators of IL6 action. Serum levels of IL6 and sIL6R (the soluble form of IL6R) are higher in several diseases such as osteoporosis or obesity. Variants at IL6R have been associated with BMI and obesity. However, IL6R is an as-yet-unexplored osteoporosis candidate gene. DESIGN In the present study we analysed two polymorphisms in the IL6R promoter, -1435 C/T (rs3887104) and -208 G/A (rs4845617), and the Asp358Ala polymorphism (rs8192284), in relation to both BMD and BMI in a cohort of 559 postmenopausal Spanish women. RESULTS The promoter polymorphisms, -1435 C/T and -208 G/A were associated with femoral neck (FN) BMD (P=0.011 and P=0.025 respectively). The C-A and T-G promoter haplotypes were also associated with FN BMD. Additionally, the Asp358Ala variant was associated with lumbar spine BMD (P=0.038). Finally, the -208 G/A polymorphism and the C-G and C-A haplotypes were associated with BMI and obesity, where GG was the risk genotype (P=0.033 for BMI; P=0.010 for obesity). CONCLUSION These data suggest that variants in the IL6R gene are not only involved in the determination of BMI but also relevant for the determination of BMD. The IL6R gene may belong to the growing list of genes known to be involved in both phenotypes.

Functional and quality-of-life results of displaced and nondisplaced proximal humeral fractures treated conservatively.

Objectives: Functional and quality-of-life outcomes of conservatively treated proximal humeral fractures. Design: Prospective study. Setting: University orthopedic department at a hospital. Patients/Participants: Seventy consecutive patients between the ages of 60 and 85 years. Intervention: Conservative treatment. Main Outcome Measurements: Functional outcome measured according to the Constant score, quality of life assessed using EuroQol-5D, and fracture pattern analyzed with x-ray and computed tomography scan. Results: All fractures consolidated uneventfully with no loss of reduction in either group. Four-part fractures obtained the worst functional results (33.66) followed by three-part fractures (54.64) and finally two-part fractures (65.88 and 71). Mild pain was expected in three- and four-part fractures, whereas two-part fractures achieved near complete pain relief. Nondisplaced fractures obtained a final Constant score of 73.58 and displaced fractures a score of 59.41 with significant differences in all Constant score items with the exception of external rotation. Although patients older than 75 years scored lower (54.63) than those younger than 75 years (70.83), there was no difference in the quality-of-life perception. Conclusion: Conservative treatment of proximal humeral fractures in those patients older than age 75 years provides good pain relief with limited functional outcome. Despite limited functional outcome, this appears to have no effect on the quality-of-life perception in the population studied. Four-part fractures present the worst results and treatment options may need to be discussed with the patient to adjust treatment to patient expectations.

Promoter 2 -1025 T/C Polymorphism in the RUNX2 Gene Is Associated with Femoral Neck BMD in Spanish Postmenopausal Women

Stimulation of bone formation is a key therapeutic target in osteoporosis. Runx2 is a runt domain transcription factor essential to osteoblast differentiation, bone remodeling, and fracture healing. Runx2 knockout mice exhibit a complete lack of ossification, while overexpression of this gene in transgenic mice results in an osteoporotic phenotype. Thus, RUNX2 is a good candidate for the genetic determination of osteoporosis. In this association study, the effects of the -330 G/T polymorphism in promoter 1 and the -1025 T/C polymorphism (rs7771980) in promoter 2 of RUNX2 were tested in relation to lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD) in a cohort of 821 Spanish postmenopausal women. The minor allele frequencies for the two polymorphisms were 0.15 and 0.07, respectively. The two polymorphisms, located more than 90 kb apart, were not in linkage disequilibrium (D′ = 0.27, r2 = 0.028). In an ANCOVA test adjusting by weight, height, age, and years since menopause, the -330 G/T polymorphism was not associated with any of the phenotypes analyzed, while we found the -1025 T/C polymorphism to be associated with FN BMD (p = 0.001). In particular, individuals carrying the TC genotype had higher mean adjusted FN BMD values than those bearing the TT genotype. Our results highlight the importance of this RUNX2 promoter 2 polymorphism in FN BMD determination.

Two-part bituberosity proximal humeral fracture: a case report.

In 1934, Codman 1 described the lines of cleavage of the head of the humerus that defined the four fragments involved in proximal humeral fractures. Later on, in 1970 Neer proposed the so-called four-segment classification based on the displacement of segments rather than in the fracture lines. As Neer stated “the purposes of the four-segment classification system were to identify every type of fracture, to document the anatomic problem and the therapeutic implications of each category, and to provide terminology that could be used to depict the pathoanatomy of each entity.” Despite the lack of reliability and reproducibility found on imaging interpretation, Neer’s classification system remains as the most world widely used among shoulder surgeons. Neer established four categories for two-part fractures: two-part anatomic neck, two-part surgical neck, two-part greater tuberosity, and two-part lesser tuberosity, the last two of them could be associated with anterior or posterior dislocation, respectively. The purpose of this report is to describe a new category of two-part proximal humeral fracture defined by the fracture and displacement of both tuberosities together.

Assessment of radiolucent lines in cemented shoulder hemi-arthroplasties: study of concordance and reproducibility

We report on the concordance and reproducibility of the evaluation of radiolucent lines in the humeral component of shoulder arthroplasty. Thirty-two shoulder prostheses were assessed independently, on two occasions, by five observers. The level of inter- and intra-observer agreement was calculated using the kappa statistic. Intra-observer agreement: the overall kappa values ranged from 0 to 0.6, meaning poor, fair and moderate agreement levels. Inter-observer agreement: when the anteroposterior (AP) views were analysed, the values obtained for the bone–cement interface ranged from 0.290 to 0.539, meaning a poor-to-moderate agreement. For the cement–implant interface, the values ranged from 0.064 to 0.684, meaning a poor-to-good agreement. When radiolucent lines of the humeral component were analysed, inter-observer agreement proved to be as low as that obtained when total hip or knee components were analysed. Intra-observer agreement showed better results.RésuméLe but de cette étude est d’évaluer les liserés du composant huméral de la prothèse d’épaule. 32 prothèses d’épaules ont été suivies de façon indépendante à deux reprises par 5 observateurs. L’évaluation a été réalisée de façon statistique en intra et en inter observateurs. l’évaluation intra observateur est classée de 0 à 0.6 (mauvais, médiocre, moyen) et pour l’évaluation inter observateur, ces valeurs sont toujours basées sur l’analyse de la radio antéro postérieure et de 0.290 à 0.539. En ce qui concerne l’analyse de l’interface ciment - implant, ces valeurs variant de 0.064 à 0.684. l’évaluation inter observateur concernant les liserés est identique à ce que l’on peut observer dans l’analyse des prothèses totales de hanche ou de genou. L’analyse intra observateur améliore encore les résultats de cette évaluation.

Morphology of the scapula relative to the reverse shoulder prosthesis

Purpose. To analyse the morphology of the scapula relative to the reverse shoulder prosthesis. Methods. Scapulas of 46 women and 27 men aged 16 to 84 (mean, 53) years with proximal humeral fractures (n=52) or recurrent antero-inferior instability (n=21) were assessed using 3-dimensional computed tomography (CT). For comparison, 108 cadaveric scapulas with unknown epidemiology were assessed using a goniometer and a caliper. The length of the glenoid neck, the angle between the glenoid surface and the upper posterior column of the scapula, and the angles between the major craneocaudal glenoid axis and (1) the base of the coracoid process and (2) the upper posterior column of the scapula were assessed. Results. The length of the glenoid neck was classified into short and long. In the respective CT and cadaveric groups, the anterior glenoid neck was short in 42% and 18% of scapulas and long in 58% and 82%, whereas the posterior glenoid neck was short in 34% and 60% of scapulas and long in 66% and 40%. The angle between the glenoid surface and the upper posterior column of the scapula was classified into types I (50°–52°) and II (62°–64°). In the respective CT and cadaveric groups, 61% and 71% of scapulas were type I and 39% and 29% were type II. All differences between groups were significant. The mean angles between the major craneocaudal glenoid axis and (1) the base of the coracoid process and (2) the upper posterior column of the scapula were 18° and 8°, respectively. Conclusion. Because of variations in scapular morphology, individualised adjustment is needed for reverse shoulder prostheses. Three-dimensional CT is valuable in preoperative planning.