Highly purified chondroitin sulfate: a literature review on clinical efficacy and pharmacoeconomic aspects in osteoarthritis treatment

Osteoarthritis (OA) is the most prevalent musculoskeletal disease and a major cause of negative relevant outcomes, associated with an ever-increasing societal burden. Pharmaceutical-grade chondroitin sulfate (CS) was repeatedly reported to reduce pain and improve function in patients with OA. This article aims to review the evidence for the role of highly purified (hp) CS (Condrosulf®, IBSA) in the treatment of OA. We collected and reported evidence concerning (1) efficacy of hpCS 800 mg/day in the treatment of OA affecting the knee, hand and hip; (2) efficacy and safety of hpCS 1200 mg/day also in the oral gel formulation; (3) the safety profile of hpCS; (4) the difference of hpCS and pharmaceutical-grade formulations versus food supplements; (5) pharmacoeconomic added value of hpCS. The data support that hpCS is an effective and safe treatment of OA, with its effect already evident at 30 days; in addition, its beneficial action is prolonged, being maintained for at least 3 months after the drug is discontinued. Full safety reports’ analyses confirm that CS is safe to use and has almost no side effects, in particular, it showed better gastrointestinal tolerance if compared with non-steroidal anti-inflammatory drugs (NSAIDs). Moreover, the therapeutic strategy has proved to be cost-effective: treatment with CS reduced the use of NSAIDs and their side effects. © 2020, The Author(s)

Nutritional status and nutritional treatment are related to outcomes and mortality in older adults with hip fracture

Malnutrition is very prevalent in geriatric patients with hip fracture. Nevertheless, its importance is not fully recognized. The objective of this paper is to review the impact of malnutrition and of nutritional treatment upon outcomes and mortality in older people with hip fracture. We searched the PubMed database for studies evaluating nutritional aspects in people aged 70 years and over with hip fracture. The total number of studies included in the review was 44, which analyzed 26,281 subjects (73.5% women, 83.6 ± 7.2 years old). Older people with hip fracture presented an inadequate nutrient intake for their requirements, which caused deterioration in their already compromised nutritional status. The prevalence of malnutrition was approximately 18.7% using the Mini-Nutritional Assessment (MNA) (large or short form) as a diagnostic tool, but the prevalence was greater (45.7%) if different criteria were used (such as Body Mass Index (BMI), weight loss, or albumin concentration). Low scores in anthropometric indices were associated with a higher prevalence of complications during hospitalization and with a worse functional recovery. Despite improvements in the treatment of geriatric patients with hip fracture, mortality was still unacceptably high (30% within 1 year and up to 40% within 3 years). Malnutrition was associated with an increase in mortality. Nutritional intervention was cost effective and was associated with an improvement in nutritional status and a greater functional recovery. To conclude, in older people, the prevention of malnutrition and an early nutritional intervention can improve recovery following a hip fracture

Comment on: The Effect of Intra-articular Hyaluronic Acid Injections and Payer Coverage on Total Knee Arthroplasty Procedures: Evidence From Large US Claims Database

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Reducing Stigma toward the Transgender Community: An Evaluation of a Humanizing and Perspective-Taking Intervention

Transgender (TG) individuals, or those whose gender identities, expressions and/or behaviors differ from their biological sex (Kirk & Kulkarni, 2006) feel there is a pervasive pattern of discrimination and prejudice directed toward them (Lombardi et al., 2001). In comparison to their heterosexual peers, LGBT youth and emerging adults are at increased risk for a host of adverse outcomes including: suicide, depression, harassment, and victimization (IOM, 2011). Stigma has been characterized as encompassing several components: labeling, making an association between the label and a negative stereotype, separating those who are different as an “out-group” and discriminating. In a recent analysis of the transgender experience, Hill (2002) described three key constructs that can be used to understand negative emotions and behaviors toward transgender individuals: transphobia – an emotional disgust toward gender non-conforming individuals; genderism – a belief that gender non-conforming individuals are pathological or disordered; gender bashing – assault or harassment of gender non-conforming individuals. Recent work on minority stress posits a distal-proximal model of stress in which a person identifies with and makes proximal, distal social attitudes that can have negative effects on their psychological well-being (Meyer, 2003). Thus, stigmatized attitudes and behaviors not only have the potential to contribute to violence or discriminatory behavior but also have a direct impact on the psychological health of the target individual. Thus, the question of how to change negative attitudes and behaviors toward TG individuals is paramount. Researchers have sought to develop interventions aimed at reducing stigma with three basic strategies identified: protest, education and contact (Corrigan & Penn, 1999). However, to date only two such strategies have garnered empirical support: contact and education. In relation to mental illness, education strategies have received limited support (Holmes et al., 1999; see Luty et al., 2007 for an exception). In contrast, contact-based interventions yield the most dramatic changes in attitudes and behaviors; contact involving media depictions have also been demonstrated to yield positive attitude change. Comparing traditional diagnosis-centered teaching about mental illness to a humanizing approach that required students to write a first-person narrative about suffering from a mental illness, Mann and Himelein (2008) found that attitudes changed only when students were required to adopt the perspective of a mentally ill individual. In their recent meta-analysis, Pettigrew and Tropp (2006) demonstrated that contact reduces prejudice and is particularly effective when it occurs under favorable conditions (e.g., conditions of equality, cooperation, and institutional support). While a wealth of research has supported the contact hypothesis related to changing negative attitudes toward ethnic minorities, the mentally ill, the homeless, gays/lesbians and other stigmatized groups, there have been a limited number of studies evaluating associations between contact and attitudes toward the TG community (Harvey, 2002; Hill & Willoughby, 2005) and no controlled studies to evaluate the efficacy of such methods. The current study extends work evaluating anti-stigma interventions to the TG community and seeks to evaluate whether attitude change will differ between participants receiving basic education about the transgender community and those who are educated about TG through media depictions of TG families and are asked to engage in a perspective-taking task. We hypothesize that participants in the humanizing condition who view a documentary and write a first-person narrative of transgender experiences will show a more significant change in transphobia, genderist attitudes and desire for social distance across time relative to participants in the education-only condition signaling less stigmatized and prejudicial attitudes at post-test. Hodson (2011) recently examined the existing contact literature and found that, consistent with Pettigrew’s (1998) focus on individual differences, intergroup contact was effective (and perhaps even more effective) among individuals who were intolerant and cognitively rigid. Religious fundamentalism has been associated with anti-homosexual sentiment (Fulton et al., 1999). Whether religiosity is similarly associated with negative attitudes toward TG individuals will be explored. Whether religiosity and prior contact with the LGBTQ community will moderate intervention outcomes will also be explored

Cost-effectiveness of buffered soluble alendronate 70 mg effervescent tablet for the treatment of postmenopausal women with osteoporosis in Italy

Summary: The use of buffered soluble alendronate 70 mg effervescent tablet, a convenient dosing regimen for bisphosphonate therapy, seems a cost-effective strategy compared with relevant alternative treatments for postmenopausal women with osteoporosis aged 60 years and over in Italy. Introduction: To assess the cost-effectiveness of buffered soluble alendronate (ALN) 70 mg effervescent tablet compared with relevant alternative treatments for postmenopausal osteoporotic women in Italy. Methods: A previously validated Markov microsimulation model was adjusted to the Italian healthcare setting to estimate the lifetime costs (expressed in €2019) per quality-adjusted life-years (QALY) of buffered soluble ALN compared with generic ALN, denosumab, zoledronic acid and no treatment. Pooled efficacy data derived from the NICE network meta-analysis were used for bisphosphonate treatments. Two treatment duration scenarios were assessed: 1 year using persistence data derived from an Italian prospective observational study including 144 and 216 postmenopausal osteoporotic women on buffered soluble ALN and oral ALN, respectively, and 3 years. Analyses were conducted for women 60–80 years of age with a bone mineral density T-score ≤ − 3.0 or with existing vertebral fractures. Results: In all simulated populations, buffered soluble ALN was dominant (more QALYs, lower costs) compared to denosumab. The cost per QALY gained of buffered soluble ALN compared to generic ALN and no treatment always falls below €20,000 per QALY gained. In the 1-year treatment scenario, zoledronic acid was associated with more QALY than buffered soluble ALN but the cost per QALY gained of zoledronic acid compared with buffered soluble ALN was always higher than €70,000, while buffered soluble ALN was dominant in the 3-year treatment scenario. Conclusion: This study suggests that buffered soluble ALN represents a cost-effective strategy compared with relevant alternative treatments for postmenopausal osteoporosis women in Italy aged 60 years and over. © 2021, The Author(s)

Implications for Fracture Healing of Current and New Osteoporosis Treatments: An ESCEO Consensus Paper

Osteoporotic fracture healing is critical to clinical outcome in terms of functional recovery, morbidity, and quality of life. Osteoporosis treatments may affect bone repair, so insights into their impact on fracture healing are important. We reviewed the current evidence for an impact of osteoporosis treatments on bone repair. Treatment with bisphosphonate in experimental models is associated with increased callus size and mineralization, reduced callus remodeling, and improved mechanical strength. Local and systemic bisphosphonate treatment may improve implant fixation. No negative impact on fracture healing has been observed, even after major surgery or when administered immediately after fracture. Experimental data for denosumab and raloxifene suggest no negative implications for bone repair. The extensive experimental results for teriparatide indicate increased callus formation, improved biomechanical strength, and greater external callus volume and total bone mineral content and density. Case reports and a randomized trial have produced mixed results but are consistent with a positive impact of teriparatide on clinical fracture healing. Studies with strontium ranelate in models of fracture healing indicate that it is associated with improved bone microstructure, callus volume, and biomechanical properties. Finally, there is experimental evidence for a beneficial effect of some of the agents currently being developed for osteoporosis, notably sclerostin antibody and DKK1 antibody. There is currently no evidence that osteoporosis treatments are detrimental for bone repair and some promising experimental evidence for positive effects on healing, notably for agents with a bone-forming mode of action, which may translate into therapeutic application

Subtrochanteric fractures after long-term treatment with bisphosphonates: a European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, and International Osteoporosis Foundation Working Group Report

Summary: This paper reviews the evidence for an association between atypical subtrochanteric fractures and long-term bisphosphonate use. Clinical case reports/reviews and case-control studies report this association, but retrospective phase III trial analyses show no increased risk. Bisphosphonate use may be associated with atypical subtrochanteric fractures, but the case is yet unproven. Introduction: A Working Group of the European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis and the International Osteoporosis Foundation has reviewed the evidence for a causal association between subtrochanteric fractures and long-term treatment with bisphosphonates, with the aim of identifying areas for further research and providing recommendations for physicians. Methods: A PubMed search of literature from 1994 to May 2010 was performed using key search terms, and articles pertinent to subtrochanteric fractures following bisphosphonate use were analysed. Results: Several clinical case reports and case reviews report a possible association between atypical fractures at the subtrochanteric region of the femur in bisphosphonate-treated patients. Common features of these ‘atypical' fractures include prodromal pain, occurrence with minimal/no trauma, a thickened diaphyseal cortex and transverse fracture pattern. Some small case-control studies report the same association, but a large register-based study and retrospective analyses of phase III trials of bisphosphonates do not show an increased risk of subtrochanteric fractures with bisphosphonate use. The number of atypical subtrochanteric fractures in association with bisphosphonates is an estimated one per 1,000 per year. It is recommended that physicians remain vigilant in assessing their patients treated with bisphosphonates for the treatment or prevention of osteoporosis and advise patients of the potential risks. Conclusions: Bisphosphonate use may be associated with atypical subtrochanteric fractures, but the case is unproven and requires further research. Were the case to be proven, the risk-benefit ratio still remains favourable for use of bisphosphonates to prevent fracture

Assessment of health claims in the field of bone: a view of the Group for the Respect of Ethics and Excellence in Science (GREES)

Health claims for food products in Europe are permitted if the nutrient has been shown to have a beneficial nutritional or physiological effect. This paper defines health claims related to bone health and provides guidelines for the design and the methodology of clinical studies to support claims

Extraskeletal benefits and risks of calcium, vitamin D and anti-osteoporosis medications

Drugs used for the prevention and the treatment of osteoporosis exert various favourable and unfavourable extra-skeletal effects whose importance is increasingly recognized notably for treatment selection. INTRODUCTION: The therapeutic armamentarium for the prevention and the treatment of osteoporosis is increasingly large, and possible extra-skeletal effects of available drugs could influence the choice of a particular compound. METHODS: The present document is the result of a national consensus, based on a systematic and critical review of the literature. RESULTS: Observational research has suggested an inverse relationship between calcium intake and cardiovascular diseases, notably through an effect on blood pressure, but recent data suggest a possible deleterious effect of calcium supplements on cardiovascular risk. Many diverse studies have implicated vitamin D in the pathogenesis of clinically important non-skeletal functions or diseases, especially muscle function, cardiovascular disease, autoimmune diseases and common cancers. The possible effects of oral or intravenous bisphosphonates are well-known. They have been associated with an increased risk of oesophageal cancer or atrial fibrillation, but large-scale studies have not found any association with bisphosphonate use. Selective oestrogen receptor modulators have demonstrated favourable or unfavourable extra-skeletal effects that vary between compounds. Strontium ranelate has a limited number of non-skeletal effects. A reported increase in the risk of venous thromboembolism is not found in observational studies, and very rare cases of cutaneous hypersensitivity reactions have been reported. Denosumab has been introduced recently, and its extra-skeletal effects still have to be assessed. CONCLUSION: Several non-skeletal effects of bone drugs are well demonstrated and influence treatment choices