Osteoblast function in patients with idiopathic osteonecrosis of the femoral head

Aims To investigate whether idiopathic osteonecrosis of the femoral head (ONFH) is related to impaired osteoblast activities. Methods We cultured osteoblasts isolated from trabecular bone explants taken from the femoral head and the intertrochanteric region of patients with idiopathic ONFH, or from the intertrochanteric region of patients with osteoarthritis (OA), and compared their viability, mineralization capacity, and secretion of paracrine factors. Results Osteoblasts from the intertrochanteric region of patients with ONFH showed lower alkaline phosphatase (ALP) activity and mineralization capacity than osteoblasts from the same skeletal site in age-matched patients with OA, as well as lower messenger RNA (mRNA) levels of genes encoding osteocalcin and bone sialoprotein and higher osteopontin expression. In addition, osteoblasts from patients with ONFH secreted lower osteoprotegerin (OPG) levels than those from patients with OA, resulting in a higher receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) ligand (RANKL)-to-OPG ratio. In patients with ONFH, osteoblasts from the femoral head showed reduced viability and mineralized nodule formation compared with osteoblasts from the intertrochanteric region. Notably, the secretion of the pro-resorptive factors interleukin-6 and prostaglandin E2 as well as the RANKL-to-OPG ratio were markedly higher in osteoblast cultures from the femoral head than in those from the intertrochanteric region. Conclusion Idiopathic ONFH is associated with a reduced mineralization capacity of osteoblasts and increased secretion of pro-resorptive factors. Cite this article: Bone Joint Res 2021;10(9):619–628.

Case Report: Infected primary hydatid cyst of the thigh

Hydatic cyst may occur in many organs such as the liver, lung, brain or heart with radiologic features of liver and lung involvement being well known. The musculo-skeletal site is infrequent accounting for 0.7–3% cases of all cases resulting from direct implantation of oncospheres more often than hematic dissemination. We report the case of an 18-year-old female student who visited our hospital because of a swelling in the posteroexternal aspect of the left thigh that had grown during the previous six months and had become tender in the previous month with setup of fever three days before admission. Superficial ultrasound and magnetic resonance imaging demonstrated a cystic mass of the posterior compartment of the thigh developed within the short chief of the biceps femoris. Serology for hydatid cyst was positive. The diagnosis of an infected hydatid cyst was suspected preoperatively, and the patient was given antibiotics and anthelminthic treatment. The cyst was then completely excised and the histopathologic exam confirmed the hydatic origin. The patient was put on oral anti-helminthics and has been on regular follow up for last twelve months with no evidence of recurrence. Hydatidosis rarely occurs in the soft tissues and the diagnosis is challenging particularly when it is secondary infected. Hydatid serology provides certainty in the diagnosis of echinococcosis when it is positive. When it’s negative, imaging (Ultrasound, Computed tomography (CT) and Magnetic resonance imaging (MRI)) may be an approach for making the diagnosis revealing the most characteristic features of hydatid cyst.

Fragility Fractures and Imminent Fracture Risk in the Spanish Population: A Retrospective Observational Cohort Study

Fragility fractures constitute a major public health problem worldwide, causing important high morbidity and mortality rates. The aim was to present the epidemiology of fragility fractures and to assess the imminent risk of a subsequent fracture and mortality. This is a retrospective population-based cohort study (n = 1369) with a fragility fracture. We estimated the incidence rate of index fragility fractures and obtained information on the subsequent fractures and death during a follow-up of up to three years. We assessed the effect of age, sex, and skeletal site of index fracture as independent risk factors of further fractures and mortality. Incidence rate of index fragility fractures was 86.9/10,000 person-years, with highest rates for hip fractures in women aged ≥80 years. The risk of fracture was higher in subjects with a recent fracture (Relative Risk(RR), 1.80; p < 0.01). Higher age was an independent risk factor for further fracture events. Significant excess mortality was found in subjects aged ≥80 years and with a previous hip fracture (hazard ratio, 3.43 and 2.48, respectively). It is the first study in Spain to evaluate the incidence of major osteoporotic fractures, not only of the hip, and the rate of imminent fracture. Our results provide further evidence highlighting the need for early treatment.

Associations between Bone Material Strength Index, Calcaneal Quantitative Ultrasound and Bone Mineral Density in Men

Objectives Impact microindentation (IMI) measures bone material strength index (BMSi) in vivo. This study investigated how IMI is associated with calcaneal quantitative ultrasound and bone densitometry parameters in men. Methods BMSi was measured on the tibial plateau using the OsteoProbe in 377 men (ages 33-96yr) from the Geelong Osteoporosis Study. Broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI) were assessed at the calcaneus using an ultrasonometer. Areal BMD was measured at several skeletal sites using dual-energy X-ray absorptiometry. Linear associations between parameters were tested using Pearson’s correlation. Multivariable regression techniques were used to determine associations between BMSi and other measures of bone, independent of confounders. Results BMSi was negatively correlated with age (r = -0.171, p=0.001), weight (r = -0.100, p=0.052) and body mass index (r = -0.187, p=0.001), and positively with height (r = +0.109, p=0.034). There was some evidence to support a positive association between BMSi and BUA (β=0.052, p=0.037), SOS (β=0.013, p=0.144) and SI (β=0.036, p=0.051). After age adjustment, this association was attenuated. No correlations were observed between BMSi and BMD at any skeletal site (r-values ranged from -0.006 to +0.079, all p&gt;0.13). Conclusion There was a small positive association between BMSi and QUS parameters, which were not independent of age. No associations were detected between BMSi and BMD. This suggests that BMSi and QUS are capturing common age-dependent properties of bone. Further research on the utility of IMI alone and complementary to conventional bone testing methods for predicting fracture risk is warranted.

A new anabolic compound, LLP2A-Ale, reserves periodontal bone loss in mice through augmentation of bone formation

Background Currently, there are no effective medications to reverse periodontal disease (PD)-induced bone loss. The objective of this study was to test a new anabolic compound, LLP2A-Ale, or with the combination treatment of mesenchymal stromal cell (MSC), in the treatment of bone loss secondary to PD. Methods PD was induced in mice by placing a ligature around the second right molar. At one week after disease induction, the mice were treated with placebo, LLP2A-Ale, MSCs, or combination of LLP2A-Ale + MSCs, and euthanized at week 4. Results We found that PD induced alveolar bone loss that was associated with reduced bone formation. LLP2A-Ale alone or in combination with MSCs sustained alveolar bone formation and reversed alveolar bone loss. Additionally, PD alone caused systemic inflammation and increased the circulating levels of G-CSF, IP-10, MIP-1a, and MIP2, which were suppressed by LLP2A-Ale +/− MSCs. LLP2A-Ale +/− MSCs increased bone formation at the peripheral skeletal site (distal femur), which was otherwise suppressed by PD. Conclusion Our findings indicated that LLP2A-Ale treatment rescued alveolar bone loss caused by PD, primarily by increasing bone formation. LLP2A-Ale also attenuated the circulating levels of a series of inflammatory cytokines and reversed the PD-induced suppression of systemic bone formation.

A new anabolic compound, LLP2A-Ale, reserves periodontal bone loss in mice through augmentation of bone formation

Background. Currently, there are no effective medications that reverse periodontal disease (PD)-induced bone loss. The objective of this study was to test a new anabolic compound, LLP2A-Ale, or with the combination treatment of mesenchymal stromal cell (MSC), in the treatment of bone loss secondary to PD. Methods. PD was induced in mice by placing a ligature around the second right molar. At one week after disease induction, the mice were treated with placebo, LLP2A-Ale, MSCs, or combination of LLP2A-Ale + MSCs, and euthanized at week 4. Results. We found that PD induced alveolar bone loss that was associated with reduced bone formation. LLP2A alone and in combination with MSCs sustained alveolar bone formation and reversed alveolar bone loss. Additionally, PD alone caused systemic inflammation and increased the circulating levels of G-CSF, IP-10, MIP-1a, and MIP2, which were suppressed by LLP2A-Ale +/- MSCs. LLP2A-Ale +/- MSCs increased bone formation at the peripheral skeletal site (distal femur), which was otherwise suppressed by PD. Conclusion. Our findings indicated that LLP2A-Ale treatment rescued alveolar bone loss caused by PD, primarily by increasing bone formation. LLP2A-Ale also attenuated the circulating levels of a series of inflammatory cytokines and reversed the PD-induced suppression of systemic bone formation.