Purpose. This pilot study aimed to explore the feasibility of scanning the human distal radius bone marrow in vivo to detect osteoporosis-related changes using magnetic resonance and evaluate whether the radius may serve as an accessible probing site for osteoporosis. This may lead in the future to the use of affordable means such as low-field MRI scanners for the monitoring of disease progression. Methods. A clinical trial was performed using a 3T MR scanner, including 26 women assigned into three study groups: healthy-premenopausal (n = 7; mean age 48.6 ± 3.5 years), healthy-postmenopausal (n = 10; mean age 54.5 ± 5.6 years), and osteoporotic-postmenopausal (n = 9; mean age 61.3 ± 5.6 years). Marrow fat composition was evaluated using T2 maps, a two-compartment model of T1, and a Dixon pulse sequence. Results. The osteoporotic group exhibited higher fat content than the other two groups and lower T2 values than the healthy-premenopausal group. Conclusions. Osteoporosis-related changes in the composition of the distal radius bone marrow may be detected in vivo using MRI protocols. The scanning protocols chosen here can later be repeated using low-field MRI scanners, thus offering the potential for early detection and treatment monitoring, using an accessible, affordable means that may be applied in small clinics. This trial is registered with <a target="_blank" href="https://clinicaltrials.gov/ct2/show/NCT03742362">MOH_2018-05-23_002247</a>, <a target="_blank" href="https://clinicaltrials.gov/ct2/show/NCT03742362">NCT03742362</a>.

Tamar K. De-Levie

Yael S. Schiffenbauer

Ido Druckmann

Vanessa Rouach

Naftali Stern

Itzhak Binderman

Uri Nevo

Quantitative MR Analysis of Changes in the Radius Bone Marrow in Osteoporosis

Gaucher disease is a rare, genetic lysosomal disorder leading to lipid accumulation and dysfunctions in multiple organs. Bone involvement is one of the most prevalent aspects of Gaucher disease. Pain, disability, and reduced quality of life remain the most frequent characteristics of bone involvement in Gaucher patients. Patients and Method. In this study, we will take into consideration data from 24 patients diagnosed with type 1 Gaucher disease. We followed them closely for six years in progress. At baseline, all patients started therapy with taliglucerase alfa at a mean dosage of 45 UI/kg; later, during the study, two of them switched their cure toward velaglucerase alfa. Before baseline evaluations, 12 patients had been treated with imiglucerase at variable duration times. At baseline, we performed an X-ray of long bones and the spine, and each year, different standard assessments were performed, such as bone pain, MRI of the vertebral spine and pelvis, and DEXA for bone density. Four patients left the study for various reasons, two of them at baseline and two others during year 3 (FU3). Results. At baseline, we had 8 children and 16 adults. The average age was 28.7 ± 16.5 SD years. The most frequent skeletal manifestations in our patients were reduction of tibial femoral space (40%), osteonecrosis (36%), and body vertebral reduction (32%). At baseline, 15 patients presented with bone pain to different degrees. Over the years, bone pain in our patients had a gradual improvement. The most dramatic bone pain improvement was seen in a patient who presented bone crises. Another impressive finding was a significant BMD improvement during six years of treatment. Our study showed a significant improvement in BMD comparing FU5 and baseline values (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42943pt" id="M1" height="10.2124pt" version="1.1" viewBox="-0.0498162 -6.78297 7.83752 10.2124" width="7.83752pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-113" d="M570 304C570 398 525 448 414 448C385 448 343 445 312 434L329 511L321 518C297 504 262 482 244 460L233 411C195 397 159 381 128 358L135 332C160 347 189 360 224 373L111 -147C97 -210 84 -218 17 -231L13 -257L254 -247L259 -218L233 -216C183 -212 177 -202 189 -142L218 -1C238 -10 266 -12 283 -12C351 3 429 48 483 105C543 168 570 242 570 304ZM482 289C482 161 380 33 304 33C278 33 248 51 233 69L303 396C326 400 352 403 369 403C428 403 482 380 482 289Z"/></g></svg> = 0.0007). Especially children demonstrated a significant improvement in BMD (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42943pt" id="M2" height="10.2124pt" version="1.1" viewBox="-0.0498162 -6.78297 7.83752 10.2124" width="7.83752pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g></svg> = 0.00061) compared to adults (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42943pt" id="M3" height="10.2124pt" version="1.1" viewBox="-0.0498162 -6.78297 7.83752 10.2124" width="7.83752pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g></svg> = 0.3673). Mean BMD change was more indicative in switched patients (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42943pt" id="M4" height="10.2124pt" version="1.1" viewBox="-0.0498162 -6.78297 7.83752 10.2124" width="7.83752pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g></svg> = 0.0142) compared to naïve patients (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42943pt" id="M5" height="10.2124pt" version="1.1" viewBox="-0.0498162 -6.78297 7.83752 10.2124" width="7.83752pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g></svg> = 0.147). Conclusions. Skeletal manifestations are very different in Gaucher type 1 patients. In our study, as a result of long-term evaluations, it was noticed that the most frequent skeletal manifestation was a reduction of tibiofemoral space. Bone pain has gradually improved in all patients. Also, BMD values have been enhanced over six years of treatment, especially in children.

Virtut Velmishi

Erjon Troja

Marjeta Tanka

Donjeta Bali

Ermira Dervishi

Afërdita Tako

Laurant Kollcaku

Paskal Cullufi

Skeletal Manifestations, Bone Pain, and BMD Changes in Albanian Type 1 Gaucher Patients Treated with Taliglucerase Alfa

Exercise is a recognized component in the prevention and therapy of osteoporosis. The present systematic review and meta-analysis aimed to determine the effect of Vitamin D (Vit-D) added to exercise versus exercise alone on bone mineral density (BMD) at the lumbar spine (LS) or hip in older adults. A systematic review based on six literature databases according to PRISMA included (a) exercise trials, with an exercise (EX) and a combined exercise + Vit-D group (EX + Vit-D), (b) intervention ≥ 6 months, and (c) BMD assessments at LS or hip. Effects sizes (MD) and 95%-confidence intervals (95%-CI) were calculated using a random-effect model that includes the inverse heterogeneity model (IVhet). Five studies with 281 participants in the EX and 279 participants in the EX + Vit-D were included. No significant differences between EX versus EX + Vit-D were observed for BMD-LS (MD: 0.002, 95%-CI: −0.033 to 0.036) or BMD-hip (MD: 0.003, 95%-CI: −0.035 to 0.042). Heterogeneity between the trial results was moderate-substantial for LS (I2 = 0%) and moderate for hip-BMD (I2 = 35%). The funnel plot analysis suggests evidence for a publication/small study bias for BMD-LS and hip results. In summary, this present systematic review and meta-analysis were unable to determine significant positive interaction of exercise and Vit-D on LS- or hip-BMD. We predominately attribute this finding to (1) the less bone-specific exercise protocols of at least two of the five studies and (2) the inclusion criteria of the studies that did not consequently focus on Vit-D deficiency. This issue should be addressed in more detail by adequately powered exercise trials with promising exercise protocols and participants with Vit-D deficiency. This trial is registered with the International Prospective Register of Systematic Reviews (PROSPERO) ID: <a target="_blank" href="https://clinicaltrials.gov/ct2/show/CRD42022309813">CRD42022309813</a>.

Cecilie Fischer

Franz Jakob

Matthias Kohl

Stephanie Kast

Simon Von Stengel

Katharina Kerschan-Schindl

Uwe Lange

Friederike Thomasius

Stefan Peters

Michael Uder

Wolfgang Kemmler

Additive Effects of Exercise and Vitamin D Supplementation (with and without Calcium) on Bone Mineral Density in Older Adults: A Systematic Review and Meta-Analysis

Background. Osteoporosis is a preventable disease that is simple and cost-effective to screen based on clinical practice guidelines, yet many patients go undiagnosed and untreated leading to increased burden of the disease. Specifically, racial and ethnic minorities have lower rates of dual energy absorptiometry (DXA) screening. Inadequate screening may lead to an increased risk of fracture, higher health care costs, and increased morbidity and mortality disproportionately experienced by racial-ethnic minority populations. Purpose. This systematic review assessed and summarized the racial and ethnic disparities that exist for osteoporosis screening by DXA. Methods. Using terms related to osteoporosis, racial and ethnic minorities, and DXA, an electronic search of databases was performed in SCOPUS, CINAHL, and PubMed. Articles were screened using predefined inclusion and exclusion criteria which dictated the final articles used in the review. Full text articles that were selected for inclusion underwent quality appraisal and data extraction. Once extracted, data from the articles were combined at an aggregate level. Results. The search identified 412 articles. After screening, a total of 16 studies were included in the final review. The overall quality of the studies included was high. Of the 16 articles reviewed, 14 identified significant disparities between racial minority and majority groups and determined that the eligible patients in racial minority groups were less likely to be referred to DXA screening. Conclusion. There is a significant disparity in osteoporosis screening among racial and ethnic minorities. Future efforts should focus on addressing these inconsistencies in screening and removing bias from the healthcare system. Additional research is required to determine the consequence of this discrepancy in screening and methods of equitizing osteoporosis care.

Anoush Calikyan

Jillian Silverberg

Katherine M. McLeod

Osteoporosis Screening Disparities among Ethnic and Racial Minorities: A Systematic Review

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.

William S. Hambright

Xiaodong Mu

Xueqin Gao

Ping Guo

Yohei Kawakami

John Mitchell

Michael Mullen

Anna-Laura Nelson

Chelsea Bahney

Haruki Nishimura

Justin Hellwinkel

Andrew Eck

Johnny Huard

The Senolytic Drug Fisetin Attenuates Bone Degeneration in the Zmpste24−/− Progeria Mouse Model

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.

Mohamed Abdelrahman Abdalla

Ricardo Rodrigues

Christian Ulbricht

Vertebral Augmentation for Painful Type 4 Osteoporotic Compression Fractures: A Comparative Study

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.

Qin Chen

Krishna M. Sinha

Benoit de Crombrugghe

Ralf Krahe

Osteoblast-Specific Overexpression of Nucleolar Protein NO66/RIOX1 in Mouse Embryos Leads to Osteoporosis in Adult Mice

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Journal of Osteoporosis provides a platform for scientists and clinicians working on the diagnosis, prevention, treatment and management of osteoporosis and other metabolic bone diseases.

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Journal of Osteoporosis maintains an Editorial Board of practicing researchers from around the world, to ensure manuscripts are handled by editors who are experts in the field of study.

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Journal of Osteoporosis - Table of contents 2023

title

Journal of Osteoporosis provides a platform for scientists and clinicians working on the diagnosis, prevention, treatment and management of osteoporosis and other metabolic bone diseases.

Journal of Osteoporosis