Age- and sex-related regional compressive strength characteristics of human lumbar vertebrae in osteoporosis

Márta Kurutz1, Judit Donáth3, Miklós Gálos2, Péter Varga1, Béla Fornet41Department of Structural Mechanics; 2Department of Construction Materials, Budapest University of Technology and Economics, Budapest, Hungary; 3Department of Reumatology, National Institute for Reumatology, Budapest, Hungary; 4Department of Radiology, County Hospital András Jósa, Nyiregyháza, HungaryObjective: To obtain the compressive load bearing and energy absorption capacity of lumbar vertebrae of osteoporotic elderly for the everyday medical praxis in terms of the simple diagnostic data, like computed tomography (CT), densitometry, age, and sex.Methods: Compressive test of 54 osteoporotic cadaver vertebrae L1 and L2, 16 males and 38 females (age range 43–93, mean age 71.6 ± 13.3 years, mean bone mineral density (BMD) 0.377 ± 0.089 g/cm2, mean T-score −5.57 ± 0.79, Z-score −4.05 ± 0.77) was investigated. Based on the load-displacement diagrams and the measured geometrical parameters of vertebral bodies, proportional, ultimate and yield stresses and strains, Young’s modulus, ductility and energy absorption capacity were determined. Three vertebral regions were distinguished: superior, central and inferior regions, but certain parameters were calculated for the upper/lower intermediate layers, as well. Cross-sectional areas, and certain bone tissue parameters were determined by image analysis of CT pictures of vertebrae. Sex- and age-related decline functions and trends of strength characteristics were determined.Results: Size-corrected failure load was 15%–25% smaller in women, proportional and ultimate stresses were about 30%–35% smaller for women in any region, and 20%–25% higher in central regions for both sexes. Young’s moduli were about 30% smaller in women in any region, and 20%–25% smaller in the central region for both sexes. Small strains were higher in males, large strains were higher in females, namely, proportional strains were about 25% larger in men, yield and ultimate strains were quasi equal for sexes, break strains were 10% higher in women. Ultimate energy absorption capacity was 10%–20% higher in men; the final ductile energy absorption capacity was quasi equal for sexes in all levels. Age-dependence was stronger for men, mainly in central regions (ultimate load, male: r = −0.66, p < 0.01, female: r = −0.52, p < 0.005; ultimate stress, male: r = −0.69, p < 0.01, female: r = −0.50, p < 0.005; Young’s modulus, male: r = −0.55, p < 0.05, female: r = −0.52, p < 0.005, ultimate stiffness, male: r = −0.58, p < 0.05, female: r = −0.35, p < 0.03, central ultimate absorbed energy density, male: r = −0.59, p < 0.015, female: r = −0.29, p < 0.08).Conclusions: For the strongly osteoporotic population (BMD < 0.4 g/cm2, T-score < −4) the statical variables (loads, stresses) showed significant correlation; mixed variables (stiffness, Young’s modulus, energy) showed moderate correlation; kinematical variables (displacements, strains) showed no correlation with age. The strong correlation of men between BMD and aging (r = −0.82, p < 0.001) and betwen BMD and strength parameters (r = 0.8–0.9, p < 0.001) indicated linear trends in age-related strength loss for men; however, the moderate correlation of women between BMD and aging (r = −0.47, p < 0.005) and between BMD and strength parameters (r = 0.4–0.5, p < 0.005) suggested the need of nonlinear (quadratic) approximation that provided the better fit in age-related strength functions of females modelling postmenopausal disproportionalities.Keywords: osteoporosis, human lumbar vertebral body, regional compressive strength, load, stress, strain, young’s modulus, energy absorption capacity, age- and sex-dependenc

Polymorphisms of CSF1 and TM7SF4 genes in a case of mild juvenile Paget's disease found using next-generation sequencing

Juvenile Paget's disease (JPD) is a rare autosomal-recessive condition. It is diagnosed in young children and characterized by a generalized increase in bone turnover, bone pain, and skeletal deformity. Our patient was diagnosed after a pathological fracture when she was 11 years old. When we first examined her at the age of 30 she had bone pain and deformity in both the femur and tibia. Serum alkaline phosphatase (ALP) level, radiology, bone scintigraphy, and densitometry were monitored. Next generation sequencing (NGS) technology, namely semiconductor sequencing, was used to determine the genetic background of JPD. Seven target genes and regions were selected and analyzed after literature review (TM7SF4, SQSTM1, TNFRSF11A, TNFRSF11B, OPTN, CSF1, VCP). No clear pathogenic mutation was found, but we detected missense polymorphisms in CSF1 and TM7SF4 genes. After treatment with zoledronic acid, infusion bone pain and ALP level decreased. We can conclude that intravenous zoledronic acid therapy is effective and safe for suppressing bone turnover and improving symptoms in JPD, but the long-term effects on clinical outcomes are unclear. Our findings also suggest that NGS may help explore the pathogenesis and aid the diagnosis of JPD

Pattern of SQSTM1 Gene Variants in a Hungarian Cohort of Paget’s Disease of Bone

Paget’s disease of bone (PDB) is characterized by focal or multifocal increase in bone turnover. One of the most well-established candidate genes for susceptibility to PDB is Sequestosome 1 (SQSTM1). Mutations in SQSTM1 have been documented among Western-European, British and American patients with PDB. However, there is no information on SQSTM1 mutation status in PDB patients from the Central- and Eastern-European regions. In this study, we conducted a mutation screening for SQSTM1 gene variants in 82 PDB patients and 100 control participants in Hungary. Mutations of SQSTM1 were detected in 18 PDB patients (21.95%); associations between genotype and clinical characteristics were also analyzed. Altogether, six different exonic alterations, including two types of UTR variants in the SQSTM1 gene, were observed in our PDB patients. Similarly, to previous genetic studies on Paget’s disease, our most commonly detected variant was the c.1175C > T (p.Pro392Leu) in nine cases (four in monostotic and five in polyostotic form). We have surveyed the germline SQSTM1 variant distribution among Hungarian patients with PDB. We also highlighted that the pattern of the analyzed disease-associated pathophysiological parameters could partially discriminate PDB patients with normal or mutant SQSTM1 genotype. However, our findings also underline and strengthen that not solely SQSTM1 stands in the background of the complex PDB etiology

Pattern of SQSTM1 Gene Variants in a Hungarian Cohort of Paget’s Disease of Bone

Paget’s disease of bone (PDB) is characterized by focal or multifocal increase in bone turnover. One of the most well-established candidate genes for susceptibility to PDB is Sequestosome 1 (SQSTM1). Mutations in SQSTM1 have been documented among Western-European, British and American patients with PDB. However, there is no information on SQSTM1 mutation status in PDB patients from the Central- and Eastern-European regions. In this study, we conducted a mutation screening for SQSTM1 gene variants in 82 PDB patients and 100 control participants in Hungary. Mutations of SQSTM1 were detected in 18 PDB patients (21.95%); associations between genotype and clinical characteristics were also analyzed. Altogether, six different exonic alterations, including two types of UTR variants in the SQSTM1 gene, wereobserved in our PDB patients. Similarly, to previous genetic studies on Paget’s disease, our most commonly detected variant was the c.1175C > T (p.Pro392Leu) in nine cases (four in monostotic and five in polyostotic form). We have surveyedthe germline SQSTM1 variant distribution among Hungarian patients with PDB. We also highlighted that the pattern of the analyzed disease-associated pathophysiological parameters could partially discriminate PDB patients with normal or mutantSQSTM1 genotype. However, our findings also underline and strengthen that not solely SQSTM1 stands in the background of the complex PDB etiolog

A Paget-kór aktuális kérdései = Paget’s disease: clinical update

A csontok Paget-kórja (osteitis deformans) a csontátépülés krónikus zavara, amelyre kórosan fokozott osteoclast- és következményesen fokozott osteoblast-aktivitás jellemző. A csontturnover felborulása következtében a csont szerkezete megváltozik, a csont deformálódik és törékennyé válik. A csont környezetében az ízület károsodik és különböző szövődmények léphetnek fel. A Paget-kór etiopatogenezisében a vírusteória bizonyítása és a genetikai háttér irányában folynak a kutatások. A Paget-kór sokszor csak a véletlen folytán kerül felfedezésre. Az emelkedett szérum alkalikus foszfatáz szint vagy a kóros csont radiológiai felvétele hívja fel a figyelmet a betegségre. A biszfoszfonátok csökkentik a betegség aktivitását az osteoclastok működésének gátlásán keresztül. Alkalmazásuk az emelkedett szérum alkalikus foszfatázzal bíró betegeknél ajánlott és azokban az esetekben, amikor szövődmények alakulhatnak ki. Orv. Hetil., 2011, 152, 1337–1346. | Paget’s disease is a chronic disorder of bone remodeling, characterized by an abnormal increase of osteoclast and, hence, osteoblast activity. The imbalance of bone turnover results in the formation of unhealthy and fragile bone. It also leads to impairment of adjacent joints and to a risk of various complications. Current research focuses on the elucidation of the etiologic role viral infection and predisposing genetic factors. Paget’s disease is commonly discovered by chance; its suspicion is raised either by high level of alkaline phosphatase or by the X-ray of the pathological bone. Bisphosphonates have proven to be effective in controlling disease activity because they inhibit osteoclast function. Their use is recommended when bone-derived serum alkaline phosphatase is high and/or when disease localizations are highly suspected for the development of complications. Orv. Hetil., 2011, 152, 1337–1346