Influence of high glucose and advanced glycation end-products (ages) levels in human osteoblast-like cells gene expression.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of osteoporotic fracture. Several factors have been identified as being potentially responsible for this risk, such as alterations in bone remodelling that may have been induced by changes in circulating glucose or/and by the presence of non-oxidative end products of glycosylation (AGEs). The aim of this study is to assess whether such variations generate a change in the gene expression related to the differentiation and osteoblast activity (OPG, RANKL, RUNX2, OSTERIX, and AGE receptor) in primary cultures of human osteoblast-like cells (hOB). METHODS: We recruited 32 patients; 10 patients had osteoporotic hip fractures (OP group), 12 patients had osteoporotic hip fractures with T2DM (T2DM group), and 10 patients had hip osteoarthritis (OA group) with no osteoporotic fractures and no T2DM. The gene expression was analyzed in hOB cultures treated with physiological glucose concentration (4.5 mM) as control, high glucose (25 mM), and high glucose plus AGEs (2 µg/ml) for 24 h. RESULTS: The hOB cultures from patients with hip fractures presented slower proliferation. Additionally, the hOB cultures from the T2DM group were the most negatively affected with respect to RUNX2 and OSX gene expression when treated solely with high glucose or with high glucose plus AGEs. Moreover, high levels of glucose induced a major decrease in the RANKL/OPG ratio when comparing the OP and the T2DM groups to the OA group. CONCLUSIONS: Our data indicates an altered bone remodelling rate in the T2DM group, which may, at least partially, explain the reduced bone strength and increased incidence of non-traumatic fractures in diabetic patients.

Study of bone mass in young daughters of women with fracture of the distal end of the radius.

The main aim was to assess whether young and healthy daughters of women with fractures of the distal end of the radius (DER) had less bone mass than the control group. In an observational study of cases and controls (1:1), the daughters of women with fractures of DER (96) were selected at the age of reaching the peak of bone mass and compared with a control group (91). All women underwent medical history, analytical determinations, and densitometry. In the case group, we found lower bone mass values at the spine and femoral neck than the control group. We also found a lower bone mass at the hips of daughters of women with 1 or more osteoporotic fractures associated with DER and at the lumbar spine in those whose mothers had densitometric osteoporosis. In conclusion, young daughters of women with fractures of DER had lower levels of bone mass density, with a possible "location-specific" occurrence based on the presence of 1 or more osteoporotic fractures associated with DER or on the presence of maternal densitometric osteoporosis.

Response to Denosumab Treatment for 2 Years in an Adolescent With Osteoradionecrosis.

Radiotherapy, an essential component of cancer treatment, is not without risk to bone, particularly to the immature or growing skeleton. Known side effects range from post-radiation osteitis to osteoradionecrosis. We report the case of a 14-year-old male patient undergoing denosumab treatment, a new antiresorptive agent, for osteoradionecrosis. The patient exhibited fractures and associated pain and functional limitations secondary to radiation for the treatment of an embryonal rhabdomyosarcoma of prostate grade III administered at age 5 years. After treatment with denosumab, the pain disappeared, bone remodeling markers dramatically declined, bone mass increased, and pathological bone scan findings resolved without adverse effects or new fractures.

Microstructural trabecular bone from patients with osteoporotic hip fracture or osteoarthritis: its relationship with bone mineral density and bone remodelling markers.

Osteoporosis (OP) and osteoarthritis (OA) are the most prevalent musculoskeletal disorders in the elderly but the relationship between them is unclear. The purposes of this study are to analyze the bone turnover markers (BTM), bone mineral density (BMD) and the structural and mechanical properties of trabecular bone in patients with OP and OA, and to explore the relationship between these two diseases. We studied 12 OP patients and 13 OA patients. We analyzed BTM (ß-CrossLaps and PINP), BMD and microstructural and biomechanical parameters (micro-CT). Our results were: OP group has higher levels of ß-CrossLaps and lower BMD at the femoral neck. Also, OP patients have a decreased volume of trabecular bone and less trabecular number, with architecture showing prevalence of rod-like trabeculae and worse connectivity than OA patients. The biomechanical parameters were worse in OP patients. BMD was correlated with almost all the structural and biomechanical parameters. Moreover, ß-CrossLaps was negatively correlated with hip BMD and with bone surface density and positively with trabecular separation. BTM, BMD and bone microstructural changes in osteoporosis are opposite to those of OA. These findings justify a less resistant bone with higher risk of fragility fractures in OP patients. These histomorphometric and biomechanical changes may be suspected by measuring of BMD and ß-CrossLaps levels.

[Age of onset of puberty and menarche in type 1 diabetic girls]. / Edad del inicio puberal y de la menarquia en niñas con diabetes tipo 1.

INTRODUCTION: Delayed pubertal maturation has been reported in girls with type 1 diabetes. OBJECTIVES: To report the age of onset of puberty and menarche in girls with type 1 diabetes diagnosed before puberty. To investigate clinical factors affecting the occurrence of puberty and menarche in this population. PATIENTS AND METHODS: A retrospective study of 38 girls with type 1 diabetes, all of them on intensive insulin therapy since diagnosis and followed up at our hospital until menarche. Age of onset of puberty and age of menarche were collected as dependent variables, and time since onset of diabetes, glycosylated hemoglobin levels, daily insulin requirements, and body mass index standard deviation score were collected as independent variables. Variables are expressed as mean ± standard deviation. Multivariate linear regression models tested the associations between dependent and independent variables. Statistical analysis was performed using SPSS software. RESULTS: Thirty-eight girls were enrolled. Age of onset of puberty was 10.4 ± 1.1 years and age of menarche, 12.6 ± 1.0 years. Time since diabetes onset influenced age at onset of puberty (ß = +0.12; p=0.047). A negative association was found between body mass index standard deviation score and age at menarche (ß=-0.39; p=0.014). CONCLUSION: Diabetes duration and body mass index were correlated with age of onset of puberty and age of menarche in girls with type 1 diabetes.

Anthropometric, bone age, and bone mineral density changes after a family-based treatment for obese children.

Our objective was to identify anthropometric, bone age, and bone mineral density (BMD) changes after a family-based treatment program for obese children. We conducted a longitudinal prospective study of 50 obese children (body mass index percentage [BMI%] > or =120%) aged 9.12 +/- 1.72 years (range 6-13) at baseline. A family-based treatment program, based on inadequate feeding style with progressive modification, aerobic physical exercise increase, active parental involvement, and the use of behavioural strategies (contracting, self-monitoring, social reinforcement), was developed during a 12-month period. Anthropometric data, lumbar spine (L2-L4) BMD by dual-energy X-ray absorptiometry, bone age (BA), bone age to chronological age ratio (BA/CA), and predicted adult height (PAH) were determined at baseline and 12 months. The statistical method used was analysis of variance and the paired Student t-test. Mean BMI standard deviation score (SDS) loss was -0.61 +/- 0.76 and BMI% loss was -5.17 +/- 9.73%. Height SDS significantly decreased, BA/CA ratio also decreased significantly, and PAH change was not significant. Lumbar spine BMD SDS and BMD% did not significantly change. A family-based treatment program was effective in obese children by reducing by 5% the BMI in 1 year and increasing the activity level. Treatment reduced growth velocity and delayed bone maturation rate without affecting PAH, reflecting a situation of previous early maturation. The treatment did not modify gaining bone mass.