Journal of Osteoporosis

Aging leads to several geriatric conditions including osteoporosis (OP) and associated frailty syndrome. Treatments for these conditions are limited and none target fundamental drivers of pathology, and thus identifying strategies to delay progressive loss of tissue homeostasis and functional reserve will significantly improve quality of life in elderly individuals. A fundamental property of aging is the accumulation of senescent cells. Senescence is a cell state defined by loss of proliferative capacity, resistance to apoptosis, and the release of a proinflammatory and anti-regenerative senescence-associated secretory phenotype (SASP). The accumulation of senescent cells and SASP factors is thought to significantly contribute to systemic aging. Senolytics—compounds which selectively target and kill senescent cells—have been characterized to target and inhibit anti-apoptotic pathways that are upregulated during senescence, which can elicit apoptosis in senescent cells and relieve SASP production. Senescent cells have been linked to several age-related pathologies including bone density loss and osteoarthritis in mice. Previous studies in murine models of OP have demonstrated that targeting senescent cells pharmacologically with senolytic drugs can reduce symptomology of the disease. Here, we demonstrate the efficacy of senolytic drugs (dasatinib, quercetin, and fisetin) to improve age-associated degeneration in bone using the Zmpste24^−/− (Z24^−/−) progeria murine system for Hutchinson–Gilford progeria syndrome (HGPS). We found that the combination of dasatinib plus quercetin could not significantly mitigate trabecular bone loss although fisetin administration could reduce bone density loss in the accelerated aging Z24^−/− model. Furthermore, the overt bone density loss observed in the Z24^−/− model reported herein highlights the Z24 model as a translational model to recapitulate alterations in bone density associated with advanced age. Consistent with the “geroscience hypothesis,” these data demonstrate the utility of targeting a fundamental driver of systemic aging (senescent cell accumulation) to alleviate a common condition with age, bone deterioration.

Background. Type 4 osteoporotic fracture (OF4), according to the classification system of the Spine Section of the German Society for Orthopaedics and Trauma (DGOU), is unstable and requires fixation as per the guidelines of the same group. We evaluated the use of stand-alone vertebral body augmentation (VBA) in pain control of OF4. Methods. This is a single-centre, in two hospitals, comparative study to evaluate the effectiveness of percutaneous vertebroplasty (PVP) and kyphoplasty (KP) in pain control of OF4. OF4 patients treated with VBA were compared to a conservatively treated control group. The two groups of OF4 were then compared to similar cohort of OF2 and OF3 patients who were treated by either VBA or expectantly. Results. A total of 78 cases were studied. VBA of OF4 showed a statistically significant better pain control than conservative treatment. The response of this group of fractures to VBA was similar to that of OF2 and 3. Conclusion. VBA can provide satisfactory pain control for OF4 patients.

In previous study, we showed that nucleolar protein 66 (NO66) is a chromatin modifier and negatively regulates Osterix activity as well as mesenchymal progenitor differentiation. Genetic ablation of the NO66 (RIOX1) gene in cells of the Prx1-expressing mesenchymal lineage leads to acceleration of osteochondrogenic differentiation and a larger skeleton in adult mice, whereas mesenchyme-specific overexpression of NO66 inhibits osteochondrogenesis resulting in dwarfism and osteopenia. However, the impact of NO66 overexpression in cells of the osteoblast lineage in vivo remains largely undefined. Here, we generated osteoblast-specific transgenic mice overexpressing a FLAG-tagged NO66 transgene driven by the 2.3 kB alpha-1type I collagen (Col1a1) promoter. We found that overexpression of NO66 in cells of the osteoblast lineage did not cause overt defects in developmental bones but led to osteoporosis in the long bones of adult mice. This includes decreased bone volume (BV), bone volume density (bone volume/total volume, BV/TV), and bone mineral density (BMD) in cancellous compartment of long bones, along with the accumulation of fatty droplets in bone marrow. Ex vivo culture of the bone marrow mesenchymal stem/stromal cells (BMSCs) from adult Col1a1-NO66 transgenic mice showed an increase in adipogenesis and a decrease in osteogenesis. Taken together, these data demonstrate a crucial role for NO66 in adult bone formation and homeostasis. Our Col1a1-NO66 transgenic mice provide a novel animal model for the mechanistic and therapeutic study of NO66 in osteoporosis.

Objectives. Both diabetes mellitus (DM) and osteoporosis are very common in older adults who reside in long-term care (LTC) facilities. Nevertheless, few studies have examined the relationship between diabetes and bone quality in this population. The purpose of this study is to determine if bone mineral density (BMD) or trabecular bone score (TBS) is a better measure of bone quality and skeletal health, in LTC residents with and without a history of DM. Methodology. In this longitudinal cohort study, we examined baseline BMD (lumbar spine, total hip, and femoral neck), TBS, DM, and functional status in 511 LTC residents who were enrolled in two ongoing randomized placebo-controlled osteoporosis clinical trials. Results. On average, participants were older than 80 years and majority were prefrail or frail. Women with DM had greater lumbar spine BMD (1.106 vs 1.017, adjusted difference ± standard error = 0.084 ± 0.023 g/cm², ) and femoral neck BMD (0.695 vs 0.651, 0.027 ± 0.013 g/cm², ), but lesser lumbar spine TBS (1.211 vs 1.266, −0.036 ± 0.016, ) compared to women without DM. Total hip BMD was also higher based on descriptive statistics (0.780 vs 0.734, ) in diabetic women, although the difference was not statistically significant. Men had similar but attenuated findings. Conclusions. Among LTC residents, those with DM have greater BMD but lower bone quality measured by TBS. TBS should be considered in assessing older patients with DM. However, further studies are required to confirm the findings with respect to fractures.

Background. The prevalence of osteoporosis is increasing in Lebanon. Aim. We evaluated the knowledge, attitudes, and practices related to osteoporosis and correlates of its perceived high risk among people living in Beirut and Mount Lebanon districts of Lebanon. Methods. This study is a cross-sectional study which consisted of 376 participants that were selected from the two districts within two or three households after two geographical areas were randomly selected from each stratum classified by education and altitude. They were then asked to fill a KAP survey on osteoporosis and provide information on factors likely related to its perceived high risk. Results. The majority of participants had a low (20.2%) and moderate (65.4%) knowledge of osteoporosis, with a higher knowledge in females than in males. A higher percentage of young people perceived it as a serious health risk than that of older people. In contrast, 85.9% participants reported drinking caffeinated beverages and 51.6% participants reported that they do not exercise. Glucose intolerance due to epigenetic and genetic factors, female sex, and older age were risk factors of a perceived high risk of osteoporosis, while any physical exercise, abstention from caffeine for 48 to 72 hours, and higher education were protective factors. Conclusion. A nationwide KAP study should be conducted; likewise, awareness campaigns should be adopted.

Developing countries are predicted to bear the burden of osteoporosis in the coming decades. The prevalence of osteoporosis in South African men is unknown, but is thought to be rare. Opportunistic screening for osteoporosis can be performed using quantitative computed tomography (CT) obtained for various clinical indications. We assessed the frequency of osteoporosis in male patients using quantitative computed tomography (CT) obtained for various clinical indications. Data were collected from abdominal and spinal CT scans performed at the radiology department of a provincial tertiary hospital between January 2019 and January 2021. The CT examinations were derived from 507 male patients (mean age, 45±15 years; 83% Black, 0.8% Coloured, 4.1% Indian and 11.2% White). In the CT scans, the region of interest was placed manually at the axial cross-sections of L1 and L3 vertebrae. Using densitometry, we calculated average bone mass density and T and Z scores. We diagnosed osteoporosis in 18.5% (n = 94) of our patients. Only 7.9% of patients younger than 50 had osteoporosis, while 35.9% of patients older than 50 years showed signs of osteoporosis. Osteoporosis was more common amongst White male patients (45.6%) and least common in Black male patients (14.4%). Indian patients had the highest prevalence of osteopenia (42.9%). We successfully used CT scans, obtained for various conditions, to identify large numbers of patients with low bone mineral density (BMD). The prevalence of osteoporosis in this sample is similar to rates reported elsewhere in Africa. Asymptomatic patients at risk of developing insufficiency fractures can be diagnosed and managed early using CT scans, thus preventing unnecessary admissions and reducing osteoporosis-related morbidity and mortality.