Goal-Directed Osteoporosis Treatment: ASBMR/BHOF Task Force Position Statement 2024.

The overarching goal of osteoporosis management is to prevent fractures. A goal-directed approach to long-term management of fracture risk helps ensure that the most appropriate initial treatment and treatment sequence is selected for individual patients. Goal-directed treatment decisions require assessment of clinical fracture history, vertebral fracture identification (using vertebral imaging as appropriate), measurement of bone mineral density (BMD) and consideration of other major clinical risk factors. Treatment targets should be tailored to each patient's individual risk profile and based on the specific indication for beginning treatment, including recency, site, number and severity of prior fractures, and BMD levels at the total hip, femoral neck, and lumbar spine. Instead of first-line bisphosphonate treatment for all patients, selection of initial treatment should focus on reducing fracture risk rapidly for patients at very high and imminent risk, such as in those with recent fractures. Initial treatment selection should also consider the probability that a BMD treatment target can be attained within a reasonable period of time and the differential magnitude of fracture risk reduction and BMD impact with osteoanabolic versus antiresorptive therapy. This position statement of the ASBMR/BHOF Task Force on Goal-Directed Osteoporosis Treatment provides an overall summary of the major clinical recommendations about treatment targets and strategies to achieve those targets based on the best evidence available, derived primarily from studies in older postmenopausal women of European ancestry.

Goal-directed treatment can help healthcare providers recommend the best treatments for individual patients to prevent fractures. The goal-directed strategy considers the site, number and recency of prior fractures. This may require imaging for spine fractures, which may not have caused pain. Treatment decisions also require bone mineral density (BMD) measurement and consideration of other major risk factors. In contrast to the standard approach, same first treatment for all, treatment selection is tailored to an individual's risk. In patients with recent fractures of the spine, hip or pelvis, fracture risk is very high and treatment should rapidly reduce that risk. For others, the target is a specific BMD level and should consider the likelihood that the treatment target can be attained within a reasonable period of time, which differs for osteoporosis medications. After initial therapy, BMD should be assessed to determine if the target has been achieved. If so, strategies should focus on maintaining BMD. If the target is not yet achieved, treatment should be intensified, or continued if it is already the most potent option. This position statement represents a consensus of expert recommendations about treatment targets and strategies to achieve those targets based on the best available evidence.

The practicality of using bone impact microindentation in a population-based study of women: A Geelong-Osteoporosis Study.

Impact microindentation (IMI) is a minimally invasive technique that allows the assessment of bone material strength index (BMSi) in vivo, by measuring the depth of a micron-sized, spherical tip into cortical bone that is then indexed to the depth of the tip into a reference material. In this study, we aimed to assess the practicality of its application in 99 women aged 42-84 yr from the Geelong Osteoporosis Study. Impact microindentation was performed in the mid-shaft of the right tibia using the OsteoProbe. Immediately following measurement, each participant was requested to rate on a Visual Analogue Scale [0-10] the level of discomfort anticipated and experienced, any initial reluctance towards the measurement and whether they were willing to repeat the measurement. Of 99 potential participants who attended this assessment phase, 55 underwent IMI measurement. Reasons for non-measurement in 44 women were existing skin conditions (n = 8, 18.2 %) and excessive soft tissue around mid-tibial region (n = 32, 72.2 %). An additional four (9.1 %) participants did not provide any reasons for declining. For 55 participants who had underwent IMI, the expectation for pain when briefed about the procedure was low (2.28 ± 2.39), as was pain experienced during the measurement (0.72 ± 1.58). Participants were not reluctant to undergo the measurement (0.83 ± 1.67), and all indicated a willingness to repeat the measurement. Results of this study showed that the IMI technique is well tolerated and accepted by women participating in the Geelong Osteoporosis Study, suggesting that the technique shows promise in a research or clinical setting.

A meta-analysis of previous falls and subsequent fracture risk in cohort studies.

The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm. INTRODUCTION: Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD). METHODS: The resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients. RESULTS: Falls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33-1.51) and men (HR 1.53, 95% CI 1.41-1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27-1.84) in men vs. HR 1.32 (95% CI 1.20-1.45) in women, P for interaction = 0.013). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. There was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men. CONCLUSIONS: A previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction.

HIV infection, bone metabolism, and fractures / Infecção pelo HIV, o metabolismo ósseo e fraturas

With the advent of high active antiretroviral therapy there was a significant improvement on HIV subjects survival. Thus, bone changes related to HIV became an important aspect of these individuals. HIV affects bone remodeling causing bone fragility. In addition, antiretroviral therapy may also negatively affect bone metabolism. Several studies describe an increased incidence of fractures in these patients when compared with controls without the disease. The European Society of AIDS (EACS), and other societies, have included guidance on management of osteoporosis in HIV-infected patients emphasizing the identification of patients with low bone mass. Supplementation of calcium and vitamin D and the use of alendronate in these individuals should be recommended on a case base.

Com o advento da terapia antirretroviral, houve uma melhora considerável na sobrevida dos indivíduos portadores do vírus HIV. Dessa forma, as alterações ósseas referentes ao HIV se tornaram um fator importante no cuidado desses indivíduos. O HIV altera o remodelamento ósseo causando fragilidade óssea. As alterações causadas por esse vírus nos linfócitos T afetam a produção de RANKL e de citocinas pró-inflamatórias levando à osteoclastogênese. Ademais, a terapia antirretroviral também pode afetar negativamente o metabolismo ósseo. Vários estudos descrevem aumento da incidência de fraturas nesses indivíduos quando comparados a controles sem a doença. Diretrizes da Sociedade Europeia de SIDA (EACS) têm orientado o manejo da osteoporose nesses sujeitos, enfatizando a identificação de pacientes com baixa massa óssea. A suplementação de cálcio e vitamina D e o uso de alendronato nesses indivíduos devem ser recomendados caso a caso.

Selective estrogen receptor modulators (SERMS) / Moduladores seletivos do receptor estrogênico (SERMs)

Hormone receptors and, specifically, estrogen receptors were described about four decades ago. For estrogens, there are two receptors, estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta). The two receptors are coded by different genes and their tissue expression varies across organs. ERalpha is predominantly expressed in reproductive tissues (uterus, breast, ovaries) liver and central nervous system, whereas ERbeta is expressed in other tissues such as bone, endothelium, lungs, urogenital tract, ovaries, central nervous system and prostate. More than seventy molecules that belong to the SERMS class have been described. There are 5 chemical groups: triphenylethylenes, benzotiophenes, tetrahydronaphtylenes, indoles and benzopyrans. All of these non-hormonal compounds are capable of activating the ER, reduce bone turnover rate and, as an antiresorptive, clearly improve bone density. Estrogens reduce bone turnover rate and, as an antiresorptive, clearly improve bone density. They are also beneficial for the relief of menopausal symptoms. An ongoing debate that extends over the decades, relates to to overall benefit/risk profile of estrogen or estrogen-progestin therapy since these therapies can increase the risk of serious health disorders, such as breast cancer. SERMs have increased our understanding of hormone-receptor regulatory mechanisms. Their development has permitted a targeted efficacy profile avoiding some of the side effects of the hormone therapy. Their clinical utility relies today mostly on the effects on breast cancer and bone.

Os receptores hormonais e especificamente os receptores estrogênicos, foram descritos há cerca de 40 anos. Para os estrógenos, existem dois tipos: o alfa (ERalfa) e os beta (ERbeta), os quais são codificados por diferentes genes e sua expressão tissular varia de tecido para tecido. O ERalfa se expressa predominantemente no aparelho reprodutivo (útero, mamas, ovários), fígado e sistema nervoso central (SNC). O ERbeta se expressa em outros tecidos como osso, endotélio, pulmões, urogenital, além dos ovários, SNC e próstata. Mais de setenta moléculas pertencentes ao grupo dos SERMs têm sido descritas, em 5 grupos químicos: trifeniletilenos, benzotiofenos, tetrahidronaftilenos, indols e benzopiranos. Todos estes compostos não hormonais são capazes de ativar o ER, reduzindo a remodelação óssea e melhorando a densidade mineral óssea. Os estrógenos reduzem a remodelação óssea e aumentam a densidade mineral óssea, como também melhoram os sintomas da menopausa. Um debate permanente existe a respeito da relação risco/benefício da terapia estrógeno-progestínica, em virtude do aumento do risco de problemas de saúde mais sérios como câncer de mama. Os SERMs aprimoraram o conhecimento sobre os mecanismos de regulação hormônio-receptor, e o seu desenvolvimento permitiu uma eficiente modalidade de ação terapêutica hormonal, evitando-se alguns dos efeitois adversos da terapia hormonal per si.