Current guidelines from the Swiss Association against Osteoporosis (SVGO) dating from 2015 recommend therapy for men and women at increased fracture risk, specifically those with a vertebral or hip ...fracture; those with bone mineral density T-score <−2.5 at spine or hip; and those with a high 10-year probability of a major osteoporotic fracture as calculated by using FRAX. However no specific treatment recommendations have been made so far in our country to guide therapy according to the baseline level of risk. We now define four risk subgroup categories (imminent and very high, high, moderate, low) and propose an algorithm for osteoporosis therapy according to the level of fracture risk.
Purpose of the review
There is an increasing body of evidence that the trabecular bone score (TBS), a surrogate of bone microarchitecture extracted from spine DXA, could play an important role in the ...management of patients with osteoporosis or at risk of fracture. The current paper reviews this published body of scientific literature on TBS and answers the most relevant clinical questions.
Recent findings
TBS has repeatedly been proven to be predictive of fragility fractures, current and future, and this is largely independent of BMD, CRF, and the FRAX, and when used in conjunction with any one of these measures, it consistently enhances their accuracy. There also is a growing body of evidence indicating that the TBS has particular advantages over BMD for specific causes of increased fracture risk, like chronic corticosteroid excess, type-2 diabetes, and chronic kidney disease, and patients being treated with anti-aromatase and primary hyperparathyroidism, conditions wherein BMD readings are often misleading.
Summary
TBS enhances performance of the FRAX tool, where its greatest utility appears to lie in its ability to accurately classify those patients whose BMD level lies close to the intervention threshold, aiding in decisions on whether treatment is warranted or not. Furthermore, TBS has also particular advantages over BMD in secondary osteoporosis. While the role of TBS with monitoring could be important as the different molecules impact logically TBS to various degrees, large clinical trials are still needed.
Abstract
Context:
Denosumab inhibits bone resorption, increases bone mineral density, and reduces fracture risk. Denosumab was approved for the treatment of osteoporosis and the prevention of bone ...loss in some oncological situations. Denosumab discontinuation is associated with a severe bone turnover rebound (BTR) and a rapid loss of bone mineral density. The clinical consequences of the BTR observed after denosumab discontinuation are not known.
Cases Description:
We report 9 women who presented 50 rebound-associated vertebral fractures (RAVFs) after denosumab discontinuation. A broad biological and radiological assessment excluded other causes than osteoporosis. These 9 cases are unusual and disturbing for several reasons. First, all vertebral fractures (VFs) were spontaneous, and most patients had a high number of VFs (mean = 5.5) in a short period of time. Second, the fracture risk was low for most of these women. Third, their VFs occurred rapidly after last denosumab injection (9–16 months). Fourth, vertebroplasty was associated with a high number of new VFs. All the observed VFs seem to be related to denosumab discontinuation and unlikely to the underlying osteoporosis or osteopenia. We hypothesize that the severe BTR is involved in microdamage accumulation in trabecular bone and thus promotes VFs.
Conclusion:
Studies are urgently needed to determine 1) the pathophysiological processes involved, 2) the clinical profile of patients at risk for RAVFs, and 3) the management and/or treatment regimens after denosumab discontinuation. Health authorities, physicians, and patients must be aware of this RAVF risk. Denosumab injections must be scrupulously done every 6 months but not indefinitely.
We studied 9 women who presented 50 vertebral fractures after denosumab discontinuation. A broad biological and radiological assessment found only the rapid rebound effect to explain this side effect.
TBS (Trabecular Bone Score) and Diabetes-Related Fracture Risk for the Manitoba Bone Density Program; Leslie, William D; Aubry-Rozier, Berengère ...
The journal of clinical endocrinology and metabolism,
2013-February, Letnik:
98, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Context:
Type 2 diabetes is associated with increased fracture risk but paradoxically greater bone mineral density (BMD). Trabecular bone score (TBS) is derived from the texture of the spine dual ...x-ray absorptiometry (DXA) image and is related to bone microarchitecture and fracture risk, providing information independent of BMD.
Objective:
This study evaluated the ability of lumbar spine TBS to account for increased fracture risk in diabetes.
Design and Setting:
We performed a retrospective cohort study using BMD results from a large clinical registry for the province of Manitoba, Canada.
Patients:
We included 29,407 women 50 years old and older with baseline DXA examinations, among whom 2356 had diagnosed diabetes.
Main Outcome Measures:
Lumbar spine TBS was derived for each spine DXA examination blinded to clinical parameters and outcomes. Health service records were assessed for incident nontraumatic major osteoporotic fractures (mean follow-up 4.7 years).
Results:
Diabetes was associated with higher BMD at all sites but lower lumbar spine TBS in unadjusted and adjusted models (all P < .001). The adjusted odds ratio (aOR) for a measurement in the lowest vs the highest tertile was less than 1 for BMD (all P < .001) but was increased for lumbar spine TBS aOR 2.61, 95% confidence interval (CI) 2.30–2.97. Major osteoporotic fractures were identified in 175 women (7.4%) with and 1493 (5.5%) without diabetes (P < .001). Lumbar spine TBS was a BMD-independent predictor of fracture and predicted fractures in those with diabetes (adjusted hazard ratio 1.27, 95% CI 1.10–1.46) and without diabetes (hazard ratio 1.31, 95% CI 1.24–1.38). The effect of diabetes on fracture was reduced when lumbar spine TBS was added to a prediction model but was paradoxically increased from adding BMD measurements.
Conclusions:
Lumbar spine TBS predicts osteoporotic fractures in those with diabetes, and captures a larger portion of the diabetes-associated fracture risk than BMD.
Osteoporosis is a common bone disease characterized by low bone mass and altered bone microarchitecture, resulting in decreased bone strength with an increased risk of fractures. In clinical ...practice, physicians can assess the risk of fracture for a patient based on several risk factors. Some such as age, weight, and history of fractures after 50 years of age, parental fracture, smoking status, and alcohol intake are incorporated into FRAX, an assessment tool that estimates the 10-year probability of hip fracture and major osteoporotic fractures based on the individual's risk factors profile. The diagnosis of osteoporosis is currently based on bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry scans. Among other widely recognized limitations of BMD is that BMD considers only the density of the bone and fails in measuring bone microarchitecture, for which novel techniques, such as trabecular bone score (TBS), have been developed. TBS is a texture parameter related to bone microarchitecture that may provide skeletal information that is not captured from the standard BMD measurement. Several studies have examined the value of TBS on predicting osteoporotic fractures. Our study aimed to summarize a review of the current scientific literature with focus on fracture risk assessment and to present both its findings and its conclusions regarding how and when TBS should be used. The existing literature indicates that low lumbar spine TBS is associated with a history of fracture and the incidence of new fracture. The effect is largely independent of BMD and of sufficient magnitude to enhance risk stratification with BMD. The TBS effect is also independent of FRAX, with likely greatest utility for those individuals whose BMD levels lie close to an intervention threshold. The clinical and scientific evidence supporting the use of TBS, with the ability of this technology to be seamlessly integrated into a daily workflow, makes TBS an attractive and useful clinical tool for physicians to improve patient management in osteoporosis. Further research is ongoing and necessary to further clarify the role of TBS in additional specific disorders.
Purpose
At denosumab discontinuation, bone turnover markers increase and the gained BMD is lost. In postmenopausal osteoporosis, there is an increased risk of spontaneous vertebral fractures (VFs) of ...about 1 to 10%, rarely described in women under denosumab for aromatase inhibitors (AI)-treated breast cancer. We aim to describe the characteristics of 15 patients under denosumab given for AI-treated early-stage breast cancer that presented VFs at its discontinuation.
Methods
Single-center retrospective case series of 15 patients. We report clinical data, dual X-ray absorptiometry values at denosumab initiation and discontinuation, and serum B-crosslaps dosage at the time of VF occurrence (before denosumab resumption).
Results
Fifteen women (66.4 ± 7.1 years at denosumab discontinuation) that received AI for 5.0 ± 0.6 years, denosumab 60 mg for 8.2 ± 2.0 doses, and developed 60 VFs at denosumab discontinuation, were followed for 24.4 ± 9.5 months. Patients suffered from 1 to 11 (mean 4.0 ± 1.9) clinical VFs within 7 to 16 months after last denosumab injection. VFs developed earlier in patients with longer denosumab treatment (
R
2
= 0.29,
p
= 0.04) and in patients without osteoporosis before denosumab (9.4 ± 2.0 vs. 13.0 ± 2.0 months;
p
= 0.005). Serum B-crosslaps at the time of VFs tended to be higher in patients with earlier VFs (
R
2
= 0.47;
p
= 0.06) or with longer denosumab treatment (
R
2
= 0.48;
p
= 0.06). Denosumab was resumed in all patients, then switched for a bisphosphonate in eight. No new VFs occurred during follow-up.
Conclusions
Despite an apparently low fracture risk, women under denosumab for AI-treated early-stage breast cancer develop spontaneous VFs at denosumab discontinuation. This risk increases with treatment duration and may be prevented by a potent bisphosphonate.
Sarcopenia, similar to hypercortisolism, is characterized by loss of muscle mass and strength. Cortisol circadian rhythm changes with aging (blunted late-day nadir values) were suggested to ...contribute to this decline. We aimed to explore the relationship between diurnal salivary cortisol values and sarcopenia diagnosis and its components in postmenopausal women. This is a cross-sectional study within the OsteoLaus population-based cohort in Lausanne (Switzerland). Participants had a body composition assessment by dual X-ray absorptiometry (DXA), a grip strength (GS) measure, and salivary cortisol measures (at awakening, 30 min thereafter, 11 AM (sc-11AM) and 8 PM (sc-8PM)). Associations between salivary cortisol and sarcopenia diagnosed by six different criteria (based on appendicular lean mass (ALM) assessed by DXA, and muscle strength by GS), and its components, were analyzed. 471 women aged > 50 years (63.0 ± 7.5) were included. Various definitions identified different participants as sarcopenic, who consistently presented higher salivary cortisol at 11 AM and/or 8 PM. There were no associations between salivary cortisol levels and ALM measures, either absolute or after correction to height squared (ALM index) or body mass index. GS was inversely correlated to sc-11AM (
r
= − 0.153,
p
< 0.001) and sc-8PM (
r
= − 0.118,
p
= 0.002). Each 10 nmol/l increase of sc-11AM, respectively sc-8PM, was associated with a GS decrease of 1.758 (SE 0.472) kg, respectively 2.929 (SE 1.115) kg. In postmenopausal women, sarcopenia is associated with higher salivary cortisol levels at 11 AM and 8 PM. An increase of daily free cortisol levels in the physiological range could participate to sarcopenia development by decreasing muscle function in postmenopausal women.
AIM OF THE STUDY: While hospitals are adopting strategies designed to increase the overall efficiency of the healthcare system, physicians are facing expanding requirements. Such changes in work ...environment add new psychosocial and physical stressors. Building on a previous quantitative time-motion study, we conducted a qualitative study to better understand the work experience of internal medicine residents.
METHODS: The study used a qualitative description approach, and was based on focus group discussions with residents. Data were analysed using reflexive thematic analysis. The study was conducted among all residents of the Internal Medicine division of a tertiary university hospital in Switzerland.
RESULTS: Time emerged as the major determinant of residents’ daily experience, which residents want to waste on no account. Shifts are perceived as a constraining succession of distinct periods, with little room for adjustments. Moreover, residents feel held back and distracted in their progression toward the end of the shift. Under time pressure, some essential professional activities, such as caring for patients and families, dealing with medical complications and talking with consultants, may be experienced as unexpected undesirable bumps on the road. Residents describe “running through” a structured day, scattered with obstacles, and resorting to “tricks of the trade” in an attempt to influence the course of the shift.
CONCLUSIONS: Time constraints are not new to medicine. However, our findings outline how time has become a constant preoccupation for internal medicine residents, permeating their daily work experience. This changing relationship with time carries the risk of undermining the foundations of clinical medicine and challenges the ability of hospitals to preserve the “sense of the profession”.
Osteoporosis care has evolved markedly over the last 50 years, such that there are now an established clinical definition, validated methods of fracture risk assessment and a range of effective ...pharmacological agents. Currently, bone-forming (anabolic) agents, in many countries, are used in those patients who have continued to lose bone mineral density (BMD), patients with multiple subsequent fractures or those who have fractured despite treatment with antiresorptive agents. However, head-to-head data suggest that anabolic agents have greater rapidity and efficacy for fracture risk reduction than do antiresorptive therapies. The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) convened an expert working group to discuss the tools available to identify patients at high risk of fracture, review the evidence for the use of anabolic agents as the initial intervention in patients at highest risk of fracture and consider the sequence of therapy following their use. This position paper sets out the findings of the group and the consequent recommendations. The key conclusion is that the current evidence base supports an “anabolic first” approach in patients found to be at very high risk of fracture, followed by maintenance therapy using an antiresorptive agent, and with the subsequent need for antiosteoporosis therapy addressed over a lifetime horizon.