Conference report

Consensus development conference: Diagnosis, prophylaxis, and treatment of osteoporosis☆

Cell therapy utilizing mesenchymal stem cells (MSCs) from healthy donors (HE-MSCs) is a promising strategy for treating osteoporotic bone defects. This study investigated the effects of interaction between HE-MSCs and MSCs from osteoporotic donors (ORX-MSCs) on osteoblast differentiation of MSCs and of HE-MSCs on bone formation in calvarial defects of osteoporotic rats.

Osteoporosis was induced by orchiectomy (ORX) and its effects on the bone were evaluated by femur microtomography (μCT) and osteoblast differentiation of bone marrow MSCs. HE- and ORX-MSCs were cocultured, and osteoblast differentiation was evaluated using genotypic and phenotypic parameters. HE-MSCs were injected into the calvarial defects of osteoporotic rats, and bone formation was evaluated by μCT, histology, and gene expression of osteoblast markers.

ORX-induced osteoporosis was revealed by reduced bone morphometric parameters and osteoblast differentiation in ORX-MSCs. HE-MSCs partially recovered the osteogenic potential of ORX-MSCs, whereas HE-MSCs were mildly affected by ORX-MSCs. Additionally, the bone morphogenetic protein and wingless-related integration site signaling pathway components were similarly modulated in cocultures involving ORX-MSCs. HE-MSCs induced meaningful bone formation, highlighting the effectiveness of cell therapy even in osteoporotic bones.

These results provide new perspectives on the development of cell-based therapies to regenerate bone defects in patients with disorders that affect bone tissue.

Some studies state that the protein intake has a protective effect against bone mass loss, while others show that the combination of low calcium intake and high protein consumption increases the risk of fractures. Perhaps this phenomenon is also altered by the consumption of vitamin D after the age 80 years. This study aimed to identify if there is an association of protein, calcium and vitamin D intake with body composition and fractures in community dwelling 80 years or older independent people.

This is a cross-sectional observational analytic study. We invited community dwelling 80 years or older independent people, with chronic diseases under control, according to the scientific guidelines. The food intake was obtained through a one-day food record (FR) and Avanutri software (4.1 version) was used to calculate the intake of total calories, calcium, protein, and other food nutrients. The body composition and bone densitometry were evaluated by whole-body Dual Energy X-ray Absorptiometry (DXA). The morphometric vertebral fractures were assessed through conventional X-ray of the vertebral, level T4 to L4, on side face position – semi quantitative technique.

One hundred and fifty-nine 80 years or older independent people, mean age 87.0 ± 3.9 years old were studied. The mean calcium intake was 834.6 ± 374.7 mg/day and vitamin D was 6.1 ± 24.3 μg/day, in both cases they were complemented by supplements to reach the recommendations. The mean protein intake was 72.9 ± 26.8 g/day, we found that 48.4% had low muscle mass; there was a frequency of 45.3% of osteoporosis; and vertebral fractures in 24.7% of them. The estimates of the logistic regression model with the outcome variable obesity and low muscle mass with reference to “low muscle mass” showed that the 80 years or older independent people who have a fracture are more likely to be obese with low muscle mass compared to those with only low muscle mass.

In the studied population of 80 years or older independent people, we observed that among all the nutrients studied, only dietary protein per g/kg/day was associated with body composition and bone mineral density, but not with fracture, although the elderly who have fracture are more likely to be obese with low muscle mass compared to those not obese with low muscle mass. More studies about nutrients intakes and its relationship with muscle and bone health in this population is necessary.

Osteoporosis can currently be diagnosed by applying the WHO classification to bone mineral density (BMD) assessed by dual-energy x-ray absorptiometry (DXA). However, skeletal factors other than BMD contribute to bone strength and fracture risk. Lumbar spine TBS, a grey-level texture measure which is derived from DXA images has been extensively studied, enhances fracture prediction independent of BMD and can be used to adjust fracture probability from FRAX® to improve risk stratification. The purpose of this International Society for Clinical Densitometry task force was to review the existing evidence and develop recommendations to assist clinicians regarding when and how to perform, report and utilize TBS. Our review concluded that TBS is most likely to alter clinical management in patients aged ≥ 40 years who are close to the pharmacologic intervention threshold by FRAX. The TBS value from L1-L4 vertebral levels, without vertebral exclusions, should be used to calculate adjusted FRAX probabilities. L1-L4 vertebral levels can be used in the presence of degenerative changes and lumbar compression fractures. It is recommended not to report TBS if extreme structural or pathological artifacts are present. Monitoring and reporting TBS change is unlikely to be helpful with the current version of the TBS algorithm. The next version of TBS software will include an adjustment based upon directly measured tissue thickness. This is expected to improve performance and address some of the technical factors that affect the current algorithm which may require modifications to these Official Positions as experience is acquired with this new algorithm.

Background: The FRAX® algorithm is a tool used to calculate the 10-year probability of fracture in patients with osteoporosis and is based the assessment of several risk factors. We assessed the performance and accuracy of the completion of the FRAX® anamnestic questionnaire by the radiographer without impact on the clinical workflow.

Methodology: We evaluated the accuracy of fracture risk calculation by the radiographer using the FRAX® algorithm before and after specific training. A total of 100 women were enrolled in the study. The radiographer preliminarily administered the FRAX® questionnaire to all subjects before the execution of the DXA examination. After the end of the examination, a radiologist administered the questionnaire to the patient. Women were divided into two groups: group A (pre-training) and group B (post-training). The radiographer in group A completed the FRAX® questionnaire for the patients before training. For group B, the same radiographer completed the FRAX® questionnaire after training. The results of the FRAX® questionnaire completed by radiographer were compared with that completed by the referring physician.

Results: Before training, radiographer's accuracy ranged from 92% (question 7, alcohol consumption) to 36% (question 6, secondary osteoporosis). After training, accuracy values improved substantially, ranging from 100% to 92%. Analysis of the absolute values of FRAX® showed that in the pre-training group data tended to be overestimated by the radiographer, with both major and fractures probabilities being significantly higher when assessed by the radiographer (12% and 5.8%, respectively). After the training, there was a marked decrease in the variation between the FRAX® data calculated by the radiographer and the radiologist.

Conclusions: The accuracy of fracture risk calculation by the radiographer using the FRAX® algorithm is significantly improved after a specific training period. This study demonstrates the importance of dedicated training radiographers on the FRAX® algorithm.

Vascular endothelial cells have recently been shown to be associated with osteogenic activity. However, the mechanism of vascular endothelial cells promoting osteogenesis is unclear. Here, we found that exosomes secreted from human microvascular endothelial cells (HMEC-1) promoted osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and inhibited adipogenic differentiation. Aged and ovariectomy mice treated with exosomes showed increased bone formation and decreased lipid accumulation in the bone marrow cavity. Additionally, we screened out novel exosomal miR-5p-72106_14 by miRNA-seq and confirmed that miR-5p-72106_14 promoted osteogenic differentiation and inhibited adipogenic differentiation of BMSCs by inhibiting STAT1. Our results suggest that vascular endothelial cell-derived exosomes are involved in BMSC differentiation and exosomal miR-5p-72106_14 is a major factor in regulating fate determination of BMSCs.