The 2021 World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Disorders (WCO-IOF-ESCEO) was hosted by London, UK, on August 26-28 (CEST) in the form of an online conference. This conference will conduct in-depth discussions on diseases such as osteoporosis, osteoarthritis and sarcopenia, so as to promote the all-round development of bone and muscle diseases.
Highlights for today
➤ The role of surgical treatment in addressing bone mass loss in patients at high risk of hip fractures
➤ Multidimensional prognostic index and fracture risk: an 8-year longitudinal cohort study in the Osteoarthritis Initiative
➤ Proportion of community-based older adults at high risk of fracture osteoporosis not using drugs to treat osteoporosis: a Canadian Longitudinal Study on Aging (CLSA)
➤ Exploration of fracture repair treatment
➤ Osteoporosis management in men
➤ Early decrease in cancellous bone mineral density in healthy men may be partially associated with decreased steroid hormones in men
First, the role of surgical treatment in solving the problem of bone mass loss in patients with high risk of hip fracture
Patients with osteoporosis have a higher risk of fractures, and Professor Serge Ferrari explained the mechanism by which this phenomenon occurs: as age increases, both cortical and cancellous bones gradually thin, and fractures occur after the load exceeds a certain limit (3000-4000 N).
There are many drugs currently available to treat osteoporosis, but for people at high risk of hip fractures, drug treatment does not meet their needs. Professor Maria Luisa Brandi introduced a new minimally invasive surgical method, AGN1 Local Osteo-enhancement Procedure (LOEP), which is developed by AgNovos and is currently under clinical study by implanting the absorbable material AGN1 (an implant consisting of calcium sulfate, calcium phosphorite and β‐‐phosphate) in the osteoporosis site. to enhance bone density at the proximal femur (Bone Mineral Density, BMD). This surgical method is a new treatment method with feasible technology, good patient acceptance and high safety, and patients can restore motor function as soon as possible after surgery. The results of several recent studies have shown that LOEP significantly increased bone density in the proximal femur during a follow-up of 2 years postoperatively, and in the most recent follow-up, there were no new fractures in the loep-treated patient group.
Professor Jo De Schepper and Professor Andreas Kurth also shared the clinical experience of performing this surgical treatment for osteoporosis patients at high risk of fracture.
Multidimensional prognostic index and fracture risk: an 8-year longitudinal cohort study in the Osteoarthritis Initiative
Frailty is often considered one of the risk factors for fragility fractures, but to date no studies have explored the predictive role of the Multidimensional Prognostic Index (MPI) on the occurrence of fragility fractures through the Comprehensive Geriatric Assessment (CGA). Based on this data gap, Professor N. Veronese et al. used data from the Osteoarthritis Initiative (OAI) to analyze the correlation between MPI and fracture risk. The MPI score is calculated primarily on 8 areas, including: living alone, Epidemiological Research Center Depression Scale (CES-D), WOMAC Osteoarthritis Average Score, Elderly Physical Activity Scale (PASE), Number of Comorbidities, Number of Concomitant Medications, Knee Injury and Osteoarthritis Outcome Score (KOOS) - Quality of Life (QoL) and Body Mass Index (BMI).
A total of 4024 people were included, of which the baseline MPI value in patients with fractures was higher than that in patients without fractures (0.42± 0.18 vs 0.40±0.17, p-value was not given). After proofreading for confounding factors, patients with MPI3 (0.67< MPI <1.00) had a higher risk of fracture compared to people with MPI1 (0< MPI <0.33) (corrected HR = 1.49; 95% CI: 1.11-2.00). This result suggests the importance of MPI in the prediction of fractures in the elderly.
Proportion of older adults at high risk of fracture in the community who do not use drugs to treat osteoporosis: a Canadian Longitudinal Study on Aging (CLSA)
Professor C. McArthur conducted a longitudinal study of older adults living in communities in Canada to estimate the proportion of older adults with osteoporosis at high risk of fractures who did not take drugs to treat osteoporosis4.
The study included a total of 28,781 patients with an average age of 70 years, with 6.2% of the subjects having a higher risk of fracture. Among the high-risk groups, 96.6% of men and 79.8% of women, respectively, did not use anti-osteoporosis drugs. As we age, the number of people using anti-osteoporosis drugs gradually increases.
The data suggest that most older adults at high risk of fracture osteoporosis do not receive anti-osteoporosis medications, and that this proportion is higher in men than in women at different ages.
Fourth, the treatment exploration of fracture repair
Patients with osteoporosis are prone to fragile fractures, of which 5% to 10% of fractures do not heal. Professor Julio Fernandes introduced the fracture recovery of patients with osteoporosis and the treatment of fracture repair.
Fracture repair refers to the restoration of the normal physiological state of cells and structures of damaged bone tissues in order to restore their biomechanical function. At present, treatment methods for fracture repair include local treatment (such as local pulsed electromagnetic field, low-intensity pulsed ultrasound, injection of autologous platelet-rich plasma, extracellular signaling molecules, etc.) and systemic therapy (such as anti-inflammatory cytokines, recombinant parathyroid hormone, monoclonal antibodies, etc.). However, so far, there are still some limitations to existing treatments5.
Regarding the future trends in fracture repair, Professor Julio Fernandes introduced the following 8 possible research directions:
1. The role of specific populations (Prx1+ cells) and their markers (Prx1)
2. Integration between the cytoskeleton and major molecular pathways
3. Factors that induce bone formation
(1) H subtype blood vessels
(2) Endogenous-exogenous composite bionic periosteum
(3) Pretreated cells (after BMP2 stimulation)
(4) In vivo isolation of native small molecules
(5) Macrophages
(6) Mulberry flavin
(7) Mesenchymal stem cells (leptin, protein network, Trb3, interleukin-1β)
4. Factors that delay the healing of fractures
(1) Inhibit the signaling α estrogen receptors
(2) Smoking
5. Diabetes and osteoporosis research
(1) Transcriptomics and proteomics methods
(2) BMP6 deficiency (35 kDa)
(3) Defects of bone stem cells
6. Evaluate an improved method that can repair cells and signaling pathways in the scab
7. A new model of fracture healing of the proximal femur
8. Co-culture system of osteoblasts and osteoclasts
Researchers have been exploring new treatments, based on a variety of bone formation induction pathways for the development of therapeutic methods. These include induction of bone formation through H subtypes of blood vessels and mesenchymal stem cells, paired-related homeobox gene 1 (Prx1) induced fractures, responses of cell signaling pathways to external mechanical stimuli, and various factors inducing or inhibiting bone formation. In addition, the more mature recombinant protein and gene therapy at this stage, and the micro-nanofiber-based artificial periosteum induced by "exogenous-endogenous" co-induction are also a highly potential treatment method5.
V. Management of osteoporosis in men
Gender differences lead to different management measures for osteoporosis. In this session, Professor Alberto Ferlin presented an in-depth analysis of the current situation, examination and treatment of osteoporosis in men.
With regard to the current situation, Professor Ferlin pointed out that osteoporosis in men is underdiagnosed (usually only after fractures), existing patients are not adequately treated, and patients receiving treatment are far less compliant with drugs than women. In addition, there is less evidence of evidence-based medicine in this field, and there is still a lot of room for research and exploration in the future. The future research directions in the field of male osteoporosis mentioned by Professor Ferlin in his speech include: the effectiveness of new drugs and sequential treatments for male osteoporosis treatment, such as bone absorption inhibitors + testosterone, bone resorption inhibitors + bone formation promoters, etc.
Osteoporosis in men is more secondary to other diseases, so the diagnosis of primary disease is of great significance for the development of individualized treatment plans. After determining the cause, lifestyle interventions and treatment of underlying conditions are the first step in the management of osteoporosis in men, and the second step is to decide which anti-osteoporosis drugs to use. Currently, drugs approved for use in men with osteoporosis in Europe and the United States include bisphosphonates, desulumab, and teriparatide 6.
In healthy men, early decrease in bone mineral density in cancellous bone may be partially associated with a decrease in steroid hormones in men
The arrangement of bone trabeculars is related to the bone loading capacity. The researchers found that in healthy men, the decline in bone density in early cancellous bone may be due in part to a decline in male sex hormones7. Professor T. Banica presented the study at the meeting.
This study is an extended study of sibling Pair Linkage Analysis of Bone Mineral Density (SIBLOS). SIBLOS is a Belgian population-based study that explored the effects of mechanical load and sex hormones and their interactions on peak bone mass in healthy men. Of the 1,001 men included in the study, 424 pairs of brothers, 23 families with three brothers, and 84 single participants whose brothers could not participate in the study8. After SIBLOS, the researchers followed the study population longitudinally, the expanded study of bone density brother linkage analysis mentioned in this conference (SIBEX - SIBlos EXtension study). SIBEX included a total of 999 participants in the SIBLOS trial, of whom 691 were re-examined after 12 years and data were collected, including serum sex hormone-binding globulin (SHBG), testosterone (T), estradiol (E2), computational free testosterone (cFT) and BMD7. The results of the study showed that the vBMD (volumetric Bone Mineral Density) of cancellous bone was reduced by 1.7% (228.9 mg/mm to 225.0 mg/mm). The subjects decreased testosterone by 14.2%, free testosterone by 19.1%, estradiol unchanged, and serum sex hormone-binding globulins by 3.0%. The researchers found through the hybrid linear model that over time, the cancellous bone vBMD was positively correlated with changes in cFT and E2 and negatively correlated with changes in SHBG.
After peak bone mass is reached, there is a mild decline in cancellous bone BMD, a trend that is partly associated with a decrease in steroid hormones in men.
bibliography:
[1] Howe JG, Hill RS, Stroncek JD, et al. Treatment of bone loss in proximal femurs of postmenopausal osteoporotic women with AGN1 local osteo-enhancement procedure (LOEP) increases hip bone mineral density and hip strength: a long-term prospective cohort study. Osteoporos Int. 2020 May;31(5):921-929.
[2] The Clinical Evaluation of the Safety of a Local Osteo-enhancement Procedure ( LOEP） Intended to Increase Bone Strength in the Proximal Femur of Women in Europe with Osteoporosis. CONFIRM Europe Safety Study - Full Text View - ClinicalTrials.gov
[3] WCO-IOF-ESCEO 2021 abstract OC11 .
[4] WCO-IOF-ESCEO 2021 abstract OC12 .
[5] Rodríguez-Merchán EC. A Review of Recent Developments in the Molecular Mechanisms of Bone Healing. Int J Mol Sci. 2021 Jan 14;22(2):767.
[6] Porcelli T, Maffezzoni F, Pezzaioli LC,et al. MANAGEMENT OF ENDOCRINE DISEASE: Male osteoporosis: diagnosis and management - should the treatment and the target be the same as for female osteoporosis? Eur J Endocrinol. 2020 Sep;183(3):R75-R93.
[7] WCO-IOF-ESCEO 2021 abstract OC30.
[8] Travison, T. G., Vesper, H. W., Orwoll, E., Wu, F., Kaufman, J. M., Wang, Y., Lapauw, B., Fiers, T., Matsumoto, A. M., & Bhasin, S. (2017). Harmonized Reference Ranges for Circulating Testosterone Levels in Men of Four Cohort Studies in the United States and Europe. The Journal of clinical endocrinology and metabolism, 102(4), 1161–1173. https://doi.org/10.1210/jc.2016-2935
Source: AMGEN Amgen
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