Multidisciplinary and Coordinated Management of Osteoporotic Vertebral Compression Fractures: Current State of the Art.

Osteoporotic vertebral compression fractures (OVCFs) present a significant health concern, affecting a substantial portion of the older adult population worldwide. This narrative review explores the prevalence, diagnostic challenges and management strategies for OVCFs. Despite the increasing incidence and impact on morbidity and mortality, existing clinical guidelines lack consistency and clear diagnostic and therapeutic recommendations. The review addresses key questions faced by physicians dealing with older adult patients experiencing acute back pain, offering insights into triage, radiological assessments and classification systems. We propose a comprehensive algorithm for clearing OVCF, considering clinical presentation, radiological findings and morphological aspects. Emphasis is placed on the importance of medically treating osteoporosis alongside OVCF management. The review encompasses relevant literature from 1993 to 2023, provides a detailed discussion on triage issues and incorporates a clinically oriented classification system developed by the German Society for Orthopaedics and Trauma. The Material and Methods section outlines the extensive literature search carried out in PUBMED, encompassing clinical and experimental studies, systematic reviews and meta-analyses. The articles retained focused mainly on answering critical questions regarding radiological assessments, imaging modalities and the presence of a specific classification system for OVCFs. The review emphasises that the evaluation and management of OVCFs necessitates a multidisciplinary approach involving spine specialists and bone disease experts. It also addresses the role of conservative versus surgical treatments, with a focus on percutaneous vertebral augmentation. The conclusion summarises the algorithm derived for use in emergency departments and general practice, aiming to streamline OVCF management, reduce unnecessary examinations and ensure optimal patient care. The algorithm recommends primary diagnosis using computed tomography, with magnetic resonance imaging reserved for specific cases. The review advocates a holistic approach, integrating medical and surgical interventions to address the complex challenges posed by OVCFs in ageing populations.

Dietary recommendations in the prevention and treatment of osteoporosis.

INTRODUCTION: This article presents the initial recommendations of the French Rheumatology Society (Société Française de Rhumatologie - SFR) and the Osteoporosis Research and Information Group (Groupe de Recherche et d'Informations sur les Ostéoporoses - GRIO) on the role of diet in the prevention and treatment of osteoporosis. METHODS: The recommendations were produced by a working group composed of rheumatologists, physician nutrition specialists and a geriatrician. Fifteen (15) questions pertaining to "daily practices" were preselected by the working group. For the literature review, the working group focussed mainly on the effects of diet on bone mineral density (BMD) and fractures, and primarily on meta-analyses of longitudinal studies and dietary intervention studies. RESULTS: A Mediterranean-type diet and the daily consumption of 2 to 3 dairy products are recommended. Together, these provide the calcium and "high quality" protein required to maintain a normal calcium-phosphorus balance and bone metabolism, and are associated with lower fracture risk. Conversely, unbalanced Western diets, vegan diets, weight-loss diets in non-overweight individuals, alcohol consumption and daily consumption of sodas are advised against. In terms of the beneficial effects on bone mineral density and fracture risk, current scientific data are either insufficient or too divergent to recommend increasing or restricting the consumption of tea or coffee, vitamins other than vitamin D, vitamin D-enriched or phytoestrogen-rich foods, calcium-enriched plant-based beverages, oral nutritional supplements, or dietary sources of prebiotics and probiotics. CONCLUSIONS: These are the first set of recommendations addressing the role of diet in the prevention and treatment of osteoporosis. More research is necessary to direct and support guidelines.

Associations of Calcium Intake and Calcium from Various Sources with Blood Lipids in a Population of Older Women and Men with High Calcium Intake.

Promoting calcium intake is a cornerstone for osteoporosis management. Some individuals limit dairy product consumption, a major calcium source, due to their high content in saturated fats and their perceived negative impact on lipid profiles. This study explored the associations of calcium from various sources with blood lipids in community-dwelling elderly (n = 717) from the GERICO cohort. Dietary calcium intake was assessed at several timepoints using a validated food frequency questionnaire (FFQ) and calcium supplement use was recorded. Blood lipids were treated as categorical variables to distinguish those with normal and abnormal levels. Increasing total calcium intake was associated with lower risks for high total cholesterol (p = 0.038) and triglycerides (p = 0.007), and low HDL-cholesterol (p = 0.010). Dairy calcium (p = 0.031), especially calcium from milk (p = 0.044) and milk-based desserts (p = 0.039), i.e., low-fat (p = 0.022) and non-fermented (p = 0.005) dairy products, were associated with a lower risk of high total cholesterol. Greater calcium intakes from total dairies (p = 0.020), milk (p = 0.020) and non-fermented dairies (p = 0.027) were associated with a lower risk of hypertriglyceridemia. No association was observed between calcium from non-dairy sources, cheese or high-fat dairies and blood lipids. Increasing calcium through supplements was associated with lower risks for hypertriglyceridemia (p = 0.022) and low HDL-cholesterol (p = 0.001), but not after adjustments. Our results suggest that higher calcium intakes from dietary sources or supplements are not adversely associated with blood lipids in the elderly, whilst total, and particularly low-fat, dairy products are valuable calcium sources potentially related to favorable lipid profiles.

Osteoporosis and HIV Infection.

Life expectancy of people living with HIV (PLWH) is now close to that of the HIV-uninfected population. As a result, age-related comorbidities, including osteoporosis, are increasing in PLWH. This narrative review describes the epidemiology of bone fragility in PLWH, changes of bone features over the course of HIV infection and their determinants, as well as the available evidence regarding the management of osteoporosis in PLWH. The risk of fracture is higher and increases about 10 years earlier compared to the general population. The classical risk factors of bone fragility are very widespread and are major determinants of bone health in this population. The majority of bone loss occurs during virus replication and during immune reconstitution at antiretroviral therapies (ART) initiation, which both increase osteoclast activity. Abnormalities in bone formation and mineralization have also been shown in histomorphometric studies in untreated PLWH. Measurement of bone mineral density (BMD) is the first line tool for assessing fracture risk in postmenopausal women, men above 50 years, and other HIV-infected patients with clinical risk factors for osteoporosis. FRAX underestimates fracture probability in PLWH. In case of indication for anti-osteoporotic drug, bisphosphonates remain the reference option. Calcium and vitamin D supplementation should be considered as ART initiation, since it may attenuate bone loss at this stage. Bone-protective ART regimens improve BMD compared to other regimens, but to a lesser extent than bisphosphonate, and without available data on their influence on the incidence of fracture.

Nutritional intake and bone health.

Osteoporotic or fragility fractures affect one in two women and one in five men who are older than 50. These events are associated with substantial morbidity, increased mortality, and an impaired quality of life. Recommended general measures for fragility fracture prevention include a balanced diet with an optimal protein and calcium intake and vitamin D sufficiency, together with regular weight-bearing physical exercise. In this narrative Review, we discuss the role of nutrients, foods, and dietary patterns in maintaining bone health. Much of this information comes from observational studies. Bone mineral density, microstructure-estimated bone strength, and trabecular and cortical microstructure are positively associated with total protein intake. Several studies indicate that fracture risk might be lower with a higher dietary protein intake, provided that the calcium supply is sufficient. Dairy products are a valuable source of these two nutrients. Hip fracture risk appears to be lower in consumers of dairy products, particularly fermented dairy products. Consuming less than five servings per day of fruit and vegetables is associated with a higher hip fracture risk. Adherence to a Mediterranean diet or to a prudent diet is associated with a lower fracture risk. These various nutrients and dietary patterns influence gut microbiota composition or function, or both. The conclusions of this Review emphasise the importance of a balanced diet including minerals, protein, and fruit and vegetables for bone health and in the prevention of fragility fractures.

Are Probiotics the New Calcium and Vitamin D for Bone Health?

PURPOSE OF REVIEW: Calcium and vitamin D supplementation is recommended for patients at high risk of fracture and/or for those receiving pharmacological osteoporosis treatments. Probiotics are micro-organisms conferring a health benefit on the host when administered in adequate amounts, likely by influencing gut microbiota (GM) composition and/or function. GM has been shown to influence various determinants of bone health. RECENT FINDINGS: In animal models, probiotics prevent bone loss associated with estrogen deficiency, diabetes, or glucocorticoid treatments, by modulating both bone resorption by osteoclasts and bone formation by osteoblast. In humans, they interfere with 25-hydroxyvitamin D levels, and calcium intake and absorption, and slightly decrease bone loss in elderly postmenopausal women, in a quite similar magnitude as observed with calcium ± vitamin D supplements. A dietary source of probiotics is fermented dairy products which can improve calcium balance, prevent secondary hyperparathyroidism, and attenuate age-related increase of bone resorption and bone loss. Additional studies are required to determine whether probiotics or any other interventions targeting GM and its metabolites may be adjuvant treatment to calcium and vitamin D or anti-osteoporotic drugs in the general management of patients with bone fragility.

[Osteoporosis]. / Ostéoporose.

Except for bisphosphonates, the duration of anti-osteoporotic treatment is not limited to 3 to 5 years. T-score between - 2.0 and - 1.5 DS might be the BMD target to reach before considering discontinuing anti-osteoporosis treatment. A rebound of bone remodeling can occur in some patients despite receiving zoledronate after denosumab discontinuation, and the monitoring of CTX is required. There is no benefit of vitamin D supplementation on musculoskeletal health in the general population, but vitamin D remains indicated in patients with vitamin D deficiency or receiving osteoporosis treatment. A sequential treatment with romosozumab during one year, a bone anabolic anti-sclerostin antibody, followed by two years of denosumab, decreases vertebral and non-vertebral fractures with rapid and substantial BMD gains after 3 years.

Le traitement de l'ostéoporose ne se limite pas à 3 ou 5 ans, hormis peut-être avec les bisphosphonates, et doit être guidé par l'évolution densitométrique en ciblant des T-scores entre - 2,0 et - 1,5 DS. En cas d'arrêt du dénosumab, une seule perfusion de zolédronate 6 ou 9 mois après la dernière injection de dénosumab peut ne pas suffire à prévenir le rebond du remodelage osseux et un suivi du marqueur de résorption CTX s'impose. Il n'y a pas de bénéfice de la supplémentation en vitamine D sur la santé musculosquelettique dans la population générale, mais celle-ci reste indiquée chez les patients déficitaires en vitamine D ou recevant des traitements de l'ostéoporose. La séquence d'un an de romosozumab, suivi de deux ans de dénosumab, permet des gains densitométriques rapides et substantiels avec une nette diminution du risque fracturaire.

Thrombin generation and fibrin clot structure after vitamin D supplementation.

OBJECTIVE: Vitamin D deficiency is associated with increased risks of arterial and venous cardiovascular events. Hypothetically, supplementation with vitamin D may lead to a less prothrombotic phenotype, as measured by global coagulation assays and fibrin clot structure. METHODS: In this prospective cohort study, we enrolled adult outpatients attending the Primary Care Division of the Geneva University Hospitals with a severe vitamin D deficiency (25-hydroxyvitamin-D3 (25-OHD) <25 nmol/L), excluding obese patients or with a recent acute medical event. We evaluated changes in coagulation times, thrombin generation assay, clot formation and clot lysis time, 25-OHD and parathormone before and 1-3 months after cholecalciferol oral supplementation with one-time 300,000 IU then 800 IU daily. Paired t-tests with a two-sided alpha of 0.05 compared absolute mean differences. RESULTS: The 48 participants had a mean age of 43.8 ± 13.8 years. After supplementation, 25-OHD levels increased from 17.9 ± 4.6 nmol/L to 62.5 ± 20.7 nmol/L 6.4 ± 3.0 weeks after inclusion. Endogenous thrombin potential and thrombin generation peak values both decreased significantly (-95.4 nM × min (95%CI -127.9 to -62.8), P < 0.001; -15.1 nM (-23.3 to -6.8), P < 0.001). The maximum absorbance by turbidimetry decreased significantly (P = 0.001) after supplementation. There was no change in clot lysis time, coagulation times or plasminogen activator inhibitor-1 and homocysteine levels. CONCLUSIONS: In severe vitamin D deficiency, a high-dose cholecalciferol supplementation was associated with a reduction in thrombin generation and an average decreased number of fibrin protofibrils per fibers and fibrin fiber size measured by turbidimetry. This suggests that severe vitamin D deficiency may be associated with a potentially reversible prothrombotic profile.

[Bone effects of bisphosphonates and denosumab treatments in breast or prostate cancer]. / Effets osseux des traitements de bisphosphonates et dénosumab en cas de cancer du sein ou de la prostate.

Two types of bone diseases can be observed in patients with breast or prostate cancer: fragility fractures related to osteoporosis, and skeletal related events (SRE) complicating bone metastases. Aromatase inhibitors, ovarian function suppression and tamoxifen use in pre-menopausal women, and androgen deprivation therapy, induce a decrease of bone mineral density and an increase of the incidence of fractures, which can be prevented by inhibitors of bone resorption at low doses. In addition, adjuvant bisphosphonates may be associated with benefits on disease free survival, especially regarding bone recurrences, in postmenopausal women with non-metastatic breast cancer. In the presence of bone metastases, inhibitors of bone resorption at higher doses and frequencies prevent SRE.

Deux complications osseuses peuvent être observées en cas de cancer du sein ou de la prostate : les fractures ostéoporotiques et les événements squelettiques osseux compliquant les métastases osseuses. Les inhibiteurs de l'aromatase, la suppression de la fonction ovarienne et le tamoxifène en préménopause, et la déprivation androgénique induisent une diminution de la densité minérale osseuse et une augmentation de l'incidence des fractures, qui peuvent être prévenues par les inhibiteurs de la résorption osseuse (IRO) à faibles doses. Par ailleurs, les bisphosphonates pourraient diminuer le risque de récidives, en particulier osseuses, chez les patientes ménopausées avec cancer du sein non métastatique. En cas de métastases osseuses, les IRO à doses et fréquences plus importantes préviennent les événements squelettiques osseux.

Glucocorticoid-induced osteoporosis: who to treat with what agent?

Among the adverse events of glucocorticoid treatment are bone loss and fractures. Despite available, effective preventive measures, many patients receiving or initiating glucocorticoid therapy are not appropriately evaluated and treated for bone health and fracture risk. Populations with, or at risk of, glucocorticoid-induced osteoporosis (GIOP) to target for these measures are defined on the basis of dose and duration of glucocorticoid therapy and bone mineral density. That patients with GIOP should be treated as early as possible is generally agreed upon; however, diversity remains in intervention thresholds and management guidelines. The FRAX(®) algorithm provides a 10-year probability of fracture that can be adjusted according to glucocorticoid dose. There is no evidence that GIOP and postmenopausal osteoporosis respond differently to treatments. Available anti-osteoporotic therapies such as anti-resorptives including bisphosphonates and the bone anabolic agent teriparatide are effective for the management of GIOP. Prevention with calcium and vitamin D supplementation is less effective than specific anti-osteoporotic treatment. Anti-osteoporotic treatment should be stopped at the time of glucocorticoid cessation, unless the patient remains at increased risk of fracture.

Microstructural alterations of trabecular and cortical bone in long-term HIV-infected elderly men on successful antiretroviral therapy.

OBJECTIVE: Progress in antiretroviral therapy (ART) has resulted in an almost normal life expectancy for HIV-infected individuals, but an increased risk of fragility fractures has been identified. We investigated the influence of long-term HIV infection on successful ART on bone microstructure in elderly men. DESIGN: A cross-sectional, case­control study. METHODS: Dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT) were performed in 28 HIV-positive men between 60 and 70 years old on successful ART. Controls were 112 HIV-negative men matched for age 4 years and BMI (4 kg/ m²). RESULTS: HIV-positive men (median CD4þ cell count, 589 cells/ml; BMI, 24.8 kg/m²) had a median duration of HIV infection of 18.2 years. Compared with HIV-negative men, they had a lower DXA-measured areal bone mineral density at total hip (3.2%, P»0.050) and ultra-distal radius (8.4%, P»0.001). At distal radius and tibia, we observed microstructural alterations with a lower total density (16%, P» 0.005 and 14.3%, P» 0.039), trabecular density (11.6%, P» 0.012 and 12.2%, P» 0.007) and cortical area (17.5%, P» 0.002 and 12.2%, P» 0.01). In addition, they had a lower trabecular number (P» 0.036), higher trabecular spacing (P» 0.027) and lower cortical thickness (19.9%; P» 0.008) at distal radius. beta-crosslaps (CTX) and vitamin D levels were higher than in controls. By multivariate analyses, HIV status, higher CTX levels, lower physical activity and estradiol levels were determinants of bone density and microstructure alterations. CONCLUSION: HIV-infected elderly men on successful ART have trabecular and cortical bone microstructure alterations associated with higher bone resorption, despite adequate vitamin D supplementation.

The "bone morphogenic proteins" pathways in bone and joint diseases: translational perspectives from physiopathology to therapeutic targets.

A large body of evidence supports an important role of bone morphogenic proteins (BMPs) pathways in skeletal development in the embryo. BMPs are also involved in skeletal homeostasis and diseases in the adult. They were first identified as major bone anabolic agents and recent advances indicate that they also regulate osteoclastogenesis and joint components via multiple cross-talks with other signaling pathways. This review attempts to integrate these data in the pathogenesis of bone and joints diseases, such as osteoporosis, fracture healing, osteoarthritis, inflammatory arthritis, or bone metastasis. The use of recombinant BMPs in bone tissue engineering and in the treatment of skeletal diseases, or future therapeutic strategies targeting BMPs signal and its regulators, will be discussed based on these considerations.