Correlation of bone density measured on CT chest with the severity of COVID-19 infection: A retrospective study.

PURPOSE: This retrospective study investigated the correlation between bone mineral density (BMD) and COVID-19 severity among COVID-19 patients who underwent chest computed tomography (CT) scans. METHODS: This study was carried out at the King Abdullah Medical Complex in Jeddah, Saudi Arabia, one of the largest COVID-19 centers in the western province. All adult COVID-19 patients who had a chest CT between January 2020 and April 2022 were included in the study. The pulmonary severity scores (PSS) and vertebral BMD measurements were obtained from the patient's CT chest. Data from the patients' electronic records were collected. RESULTS: The average patient age was 56.4 years, and most (73.5%) patients were men. Diabetes (n = 66, 48.5%), hypertension (n = 56, 41.2%), and coronary artery disease (n = 17, 12.5%) were the most prevalent comorbidities. Approximately two-thirds of hospitalized patients required ICU admission (64%), and one-third died (30%). The average length of stay in the hospital was 28.4 days. The mean CT pneumonia severity score (PSS) was 10.6 at the time of admission. Patients with lower vertebral BMD (< = 100) numbered 12 (8.8%), while those with higher vertebral BMD (>100) numbered 124 (91.2%). Only 46 out of the total survived patients (n = 95) were admitted to the ICU versus all deceased (P<0.01). The logistic regression analysis revealed that an elevated PSS upon admission resulted in a reduced chance of survival. Age, gender, and BMD did not predict survival chances. CONCLUSION: The BMD had no prognostic advantage, and the PSS was the significant factor that could have predicted the outcome.

Social isolation through single housing negatively affects trabecular and cortical bone in adult male, but not female, C57BL/6J mice.

Social isolation is a potent form of psychosocial stress and is a growing public health concern, particularly among older adults. Even prior to the onset of the COVID-19 pandemic, which has significantly increased the prevalence of isolation and loneliness, researchers have been concerned about a rising "epidemic" of loneliness. Isolation is associated with an increased risk for many physical and mental health disorders and increased overall mortality risk. In addition to social isolation, older adults are also at greater risk for osteoporosis and related fractures. While researchers have investigated the negative effects of other forms of psychosocial stress on bone, including depression and PTSD, the effects of social isolation on bone have not been thoroughly investigated. The aim of this study was to test the hypothesis that social isolation would lead to bone loss in male and female C57BL/6J mice. 16-week-old mice were randomized into social isolation (1 mouse/cage) or grouped housing (4 mice/cage) for four weeks. Social isolation significantly decreased trabecular (BV/TV, BMD, Tb. N., Tb. Th.) and cortical bone (Ct.Th., Ct.Ar., Ct.Ar./Tt.Ar., pMOI) parameters in male, but not female mice. Isolated male mice had signs of reduced bone remodeling represented by reduced osteoblast numbers, osteoblast-related gene expression and osteoclast-related gene expression. However, isolated females had increased bone resorption-related gene expression, without any change in bone mass. Overall, our data suggest that social isolation has negative effects on bone in male, but not female mice, although females showed suggestive effects on bone resorption. These results provide critical insight into the effects of isolation on bone and have key clinical implications as we grapple with the long-term health impacts of the rise in social isolation related to the COVID-19 pandemic.

COVID-19 and bone health.

A few patients who have recovered from COVID-19 develop persistent or new symptoms that last for weeks or months; this is called "long COVID" or "post-COVID-19 syndrome." Over time, awareness of the short- and long-term consequences of COVID-19 has increased. The pulmonary consequences are now fairly well established, but little is known about the extrapulmonary system of COVID-19, particularly its effects on bones. Current evidence and reports indicate a direct relationship between SARS-CoV-2 infection and bone health, with SARS-CoV-2 having a significant negative effect on bone health. In this review, we analyzed the impact of SARS-CoV-2 infection on bone health and assessed the impact of COVID-19 on the diagnosis and treatment of osteoporosis.

Safety and effectiveness of once-yearly zoledronic acid in Japanese osteoporosis patients: three-year post-marketing surveillance.

INTRODUCTION: Zoledronic acid (5 mg; ZOL), a once-yearly bisphosphonate, reduces osteoporotic fractures and increases bone mineral density (BMD). This 3-year post-marketing surveillance examined its real-world safety and effectiveness. MATERIALS AND METHODS: This prospective, observational study included patients who started ZOL for osteoporosis. Data were assessed at baseline, 12, 24, and 36 months for safety and effectiveness. Treatment persistence, potentially related factors, and persistence before and after the COVID-19 pandemic started were also investigated. RESULTS: The safety analysis and effectiveness analysis sets included 1406 and 1387 patients, respectively, with mean age of 76.5 years. Adverse reactions (ARs) occurred in 19.35% of patients, with an acute-phase reaction in 10.31, 1.01, and 0.55% after the first, second, and third ZOL infusions. Renal function-related ARs, hypocalcaemia, jaw osteonecrosis, and atypical femoral fracture occurred in 1.71, 0.43, 0.43, and 0.07% of patients, respectively. Three-year cumulative fracture incidences were 4.44% for vertebral, 5.64% for non-vertebral, and 9.56% for clinical fractures. BMD increased by 6.79, 3.14, and 1.78% at the lumbar spine, femoral neck, and total hip, respectively, after 3-year treatment. Bone turnover markers remained within reference ranges. Treatment persistence was 70.34% over 2 years and 51.71% over 3 years. Male, age ≥ 75 years, no previous medicines for osteoporosis, no concomitant medicines for osteoporosis, and inpatient at the first infusion were related to discontinuation. There was no significant difference in the persistence rate between before and after the COVID-19 pandemic (74.7% vs. 69.9%; p = 0.141). CONCLUSION: This 3-year post-marketing surveillance confirmed the real-world safety and effectiveness of ZOL.

Cytotoxic chemotherapy is associated with decreased bone mineral density in postmenopausal women with early and locally advanced breast cancer.

PURPOSE: The burden and mechanisms of endocrine therapy-related bone loss have been studied in detail. However, there is limited data regarding cytotoxic chemotherapy's impact on bone health. There are no definitive guidelines for bone mineral density (BMD) monitoring and treatment with bone-modifying agents during cytotoxic chemotherapy. The study's primary objective was to evaluate the changes in BMD and fracture risk assessment tool (FRAX) scores among breast cancer women on cytotoxic chemotherapy. METHODS: One hundred and nine newly diagnosed early and locally advanced postmenopausal breast cancer patients planned for anthracycline and taxane-based chemotherapy were recruited prospectively during the study period from July 2018 to December 2021. BMD of the lumbar spine, the femoral neck, and the total hip were assessed by dual-energy X-ray absorptiometry scan. BMD and FRAX scores were evaluated at baseline, end of chemotherapy, and 6 months of follow-up. RESULTS: The median age of the study population was 53 (45-65) years. Early and locally advanced breast cancers were seen in 34 (31.2%) and 75 (68.8%) patients, respectively. The duration of follow-up between two BMD measurements was 6 months. The percentage of decrease in BMD at the lumbar spine, femoral neck, and total hip were - 2.36 ± 2.90, - 2.63 ± 3.79, and - 2.08 ± 2.80, respectively (P-value = 0.0001). The median risk of major osteoporotic fracture (MOF) at 10 years (FRAX score) increased from 1.7 (1.4) to 2.7% (2.4) (P-value = 0.0001). CONCLUSION: This prospective study in postmenopausal breast cancer women shows a significant association of cytotoxic chemotherapy with the worsening of bone health in terms of BMD and FRAX score.

Discontinuing Denosumab: Can It Be Done Safely? A Review of the Literature.

Denosumab, which has been approved for the treatment of osteoporosis since 2010, is a fully humanised monoclonal antibody against a cytokine, receptor activator of nuclear factor kappa B ligand (RANKL), involved in bone resorption. Continued use of denosumab results in a potent and sustained decrease in bone turnover, an increase in bone mineral density (BMD), and a reduction in vertebral and hip fractures. The anti-resorptive effects of denosumab are reversible upon cessation, and this reversal is accompanied by a transient marked increase in bone turnover that is associated with bone loss, and of concern, an increased risk of multiple vertebral fractures. In this review, we outline the effects of denosumab withdrawal on bone turnover markers, BMD, histomorphometry, and fracture risk. We provide an update on recent clinical trials that sought to answer how clinicians can transition away from denosumab safely with follow-on therapy to mitigate bone loss and summarise the recommendations of various international guidelines.

BEING: Bone Health in Aging Women with HIV: Impact of Switching Antiretroviral Therapy on Bone Mineral Density During the Perimenopausal Period.

Menopause is a high-risk period for osteoporosis, which may be exacerbated by HIV and/or antiretroviral therapy (ART). Our goal was to study the impact of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) on bone mineral density (BMD) in peri- and early postmenopausal women living with HIV. This is a randomized international multicenter study of an early versus delayed (48-week) switch. BMD was measured by dual energy X-ray absorptiometry scan. Thirty-four women were enrolled: 19 in the immediate and 15 in the delayed switch arm from September 2017 to April 2019; 30 completed the 96-week protocol. The study closed for futility during the COVID-19 pandemic. The median (intraquartile range [IQR]) age was 51 years (47, 53), with a median (IQR) of 16.5 years (14, 23) since HIV diagnosis, median (IQR) 14 years (11, 20) of ART, and mean 8.6 years TDF. At enrollment, TDF was used in combination with a boosted protease inhibitor (n = 7), a non-nucleoside reverse transcriptase inhibitor (n = 13), an integrase inhibitor (n = 11), or more than one ART class (n = 3). The median (95% confidence interval [CI]) percentage change in BMD at the lumbar spine from 0 to 48 weeks in the immediate switch group was 1.97% (-1.15 to 5.49) compared with a median (95% CI) decrease of 2.32% (-5.11 to 0.19) in the delayed arm. The median (95% CI) percentage change in BMD from 0 to 96 weeks was 2.33% (0-4.51) in the immediate arm compared with 0.70% (-3.19 to 2.47) in the delayed arm. We demonstrated a trend to increased BMD at the lumbar spine after a switch from TDF to TAF in peri- and early postmenopausal women living with HIV. Clinical Trials.gov: NCT02815566.

Long-term implications of COVID-19 on bone health: pathophysiology and therapeutics.

BACKGROUND: SARS-CoV-2 is a highly infectious respiratory virus associated with coronavirus disease (COVID-19). Discoveries in the field revealed that inflammatory conditions exert a negative impact on bone metabolism; however, only limited studies reported the consequences of SARS-CoV-2 infection on skeletal homeostasis. Inflammatory immune cells (T helper-Th17 cells and macrophages) and their signature cytokines such as interleukin (IL)-6, IL-17, and tumor necrosis factor-alpha (TNF-α) are the major contributors to the cytokine storm observed in COVID-19 disease. Our group along with others has proven that an enhanced population of both inflammatory innate (Dendritic cells-DCs, macrophages, etc.) and adaptive (Th1, Th17, etc.) immune cells, along with their signature cytokines (IL-17, TNF-α, IFN-γ, IL-6, etc.), are associated with various inflammatory bone loss conditions. Moreover, several pieces of evidence suggest that SARS-CoV-2 infects various organs of the body via angiotensin-converting enzyme 2 (ACE2) receptors including bone cells (osteoblasts-OBs and osteoclasts-OCs). This evidence thus clearly highlights both the direct and indirect impact of SARS-CoV-2 on the physiological bone remodeling process. Moreover, data from the previous SARS-CoV outbreak in 2002-2004 revealed the long-term negative impact (decreased bone mineral density-BMDs) of these infections on bone health. METHODOLOGY: We used the keywords "immunopathogenesis of SARS-CoV-2," "SARS-CoV-2 and bone cells," "factors influencing bone health and COVID-19," "GUT microbiota," and "COVID-19 and Bone health" to integrate the topics for making this review article by searching the following electronic databases: PubMed, Google Scholar, and Scopus. CONCLUSION: Current evidence and reports indicate the direct relation between SARS-CoV-2 infection and bone health and thus warrant future research in this field. It would be imperative to assess the post-COVID-19 fracture risk of SARS-CoV-2-infected individuals by simultaneously monitoring them for bone metabolism/biochemical markers. Importantly, several emerging research suggest that dysbiosis of the gut microbiota-GM (established role in inflammatory bone loss conditions) is further involved in the severity of COVID-19 disease. In the present review, we thus also highlight the importance of dietary interventions including probiotics (modulating dysbiotic GM) as an adjunct therapeutic alternative in the treatment and management of long-term consequences of COVID-19 on bone health.

COVID-19 illness and treatment decrease bone mineral density of surviving hospitalized patients.

OBJECTIVE: The number patients surviving COVID-19 hospitalization is steadily increasing. Follow-up management for these patients relies on an understanding of the long-term effects of COVID-19. Specifically, there are insufficient data about the lasting effects of COVID-19 on bone health. We aim in this study to evaluate whether COVID-19 illness and treatment adversely affect the bone health of surviving patients. PATIENTS AND METHODS: We assessed the bone mineral density (BMD) of hospitalized COVID-19 patients at diagnosis and at follow-up visits. Using the chest computed tomography (CT) scans of patients that were obtained for clinical management at diagnosis and follow-up visits, BMD was retrospectively measured by quantitative CT. The effect of COVID-19 severity markers and treatment-related factors on BMD were also assessed. RESULTS: BMD decreased by a mean of 8.6% (± 10.5%) from diagnosis to follow-up. The follow-up visits occurred at a mean of 81 (± 48) days after hospital discharge. The BMD decrease was significantly greater than expected for age-related annual BMD loss. The osteoporosis ratio increased two-fold after hospitalization for COVID-19 because of this substantial bone loss. On multivariable linear regression, only severity of COVID-19 pneumonia on initial chest CT and total steroid dose were predictive of change in BMD after COVID-19 hospitalization. CONCLUSIONS: Secondary osteoporosis may occur as a post-acute sequela of COVID-19. Therefore, the bone health status of patients surviving COVID-19 hospitalization should be monitored closely at follow-up visits, to facilitate the prevention and early treatment of osteoporosis complications.

No Changes in Body Composition in NCAA Division I Collegiate Football Players because of COVID-19 Restrictions.

ABSTRACT: Czeck, MA, Roelofs, EJ, Evanoff, NG, and Dengel, DR. No Changes in body composition in NCAA Division I Collegiate Football Players due to COVID-19 restrictions. J Strength Cond Res 36(6): 1749-1752, 2022-The purpose of this study was to explore the impact of coronavirus disease 2019 (COVID-19) restrictions on body composition, assessed by dual x-ray absorptiometry (DXA), between the 2020 postseason (pre-COVID-19 restrictions) and the 2021 postseason (post-COVID-19 restrictions) in collegiate football players (n = 50). In addition, a subset of athletes (n = 23) was used to explore body composition variables across 4 postseason time points. Body composition variables assessed were total and regional body fat percent, total mass, lean mass, fat mass, bone mineral content, bone mineral density, and visceral adipose tissue mass. Paired t-tests were used to determine differences between the 2020 postseason and the 2021 postseason in body composition variables. Analysis of variance with Tukey HSD post hoc tests assessed significant differences in total and regional body composition across 4 years while adjusting for multiple comparisons. There were no significant differences (p > 0.05) between postseason 2020 and postseason 2021 for all measures of body composition. In a subset of athletes, body composition was analyzed over a 4-year period of time. There were no significant differences between all 4 time points for all measures of body composition. In conclusion, body composition variables in this study's subjects were not affected because of coronavirus disease 2019 restrictions or over 4 years of their collegiate football career.

Body composition of NCAA division I football players pre- and post-COVID-19 stay-at-home advisory.

BACKGROUND: The COVID-19 pandemic forced collegiate athletes to train at home, without access to facilities. The purpose of this study was to evaluate the effect of the COVID-19 stay-at-home order on body composition of Division I Football Players, with a secondary aim to evaluate these changes between players with "higher" (>25 kg/m2) and "lower" (<25 kg/m2) Fat-Free Mass Index (kg/m2). METHODS: Body composition of 29 NCAA Division I Football Players (age=21.0±10 yr, Ht=186.7±5.6 cm, body mass=110.5±22.8 kg) were measured spring season (February) and prior to preseason (June). Whole body dual-energy X-ray absorptiometry scans were used to determine regional (arms, legs, trunk) and total body fat mass (FM), lean mass (LM), and fat-free mass (FFM). Fat-Free Mass Index (FFMI) was calculated as (LM+bone mineral content [BMC])/height2); participants were stratified by FFMI higher (N.=16) and lower (N.=13). RESULTS: Total LM (mean difference±standard error: 0.80±1.65 kg, P=0.016) increased from pre- to post-COVID stay-at-home. No significant changes in total FM were seen. Players with lower FFMI showed a significant decrease in trunk FM (-0.55±0.19 kg, P=0.016). Players with higher FFMI showed a significant increase in total LM (0.96±0.42 kg, P=0.038). CONCLUSIONS: These results suggest no detrimental effect on body composition.

Characteristics of Interventions to Improve Bone Health in Children With Cerebral Palsy: A Systematic Review.

PURPOSE: A systematic review evaluated exercise parameters and ages that produced the most improvement in bone among individuals with cerebral palsy (CP) ages 3 to 21 years. METHODS: PubMed, Scopus, Ebscohost, and Web of Science identified potential articles. Covidence was used to identify eligible citations and assess bias. The osteogenic index (OI) was used to evaluate intervention parameters. RESULTS: The database search identified 312 citations. Twelve full-text articles were included. A 1-hour calisthenic exercise program performed 2 to 3 times a week for 8 months targeting each body region had the highest effect size and a substantial OI. Most of the interventions reviewed had low OIs. Activities of longer duration and greater intensity had greater OIs and prepubertal age-enhanced treatment effects. CONCLUSION: Bone interventions for individuals with CP have low OIs, and principles of mechanostat theory should be applied to exercise dosing.

The Multi-Modal Risk Analysis and Medical Prevention of Lumbar Degeneration, Fatigue, and Injury Based on FEM/BMD for Elderly Chinese Women Who Act as Stay-Home Grandchildren Sitters.

Background: An increasing number of Chinese elderly women stay at home and act as grandchildren sitters. In consequence of the frequent load-bearing, chronic lumbar fatigue probably caused a higher risk of lumbar degeneration, fatigue, and injury which has become one of the most important aging and health problems in China. In this study, a multi-mode lumbar finite element model (FEM) with specific bone mineral density (BMD) were developed and validated for further spine injury prevention and control. Methods: The material properties of lumbar vertebra were modified according to degenerated bone mineral density, and geometry was adjusted based on intervertebral disc height. The motion of lifting children was simulated by a 76 year-old Chinese women's FEM, and the stress distribution was calculated and predicted. Results: The pressure of L5-S intervertebral disc in the bending 3-year-old dummy lifting posture was significantly higher than the same posture without lifting, the maximum effective stress of endplate cartilage in the upright child lifting posture was 1.6 times that of the bending without lifting posture. And the fatigue risk limitation frequency of the upright with dummy posture was predicted with the functional equation of fatigue and stress which was deduced by genetic algorithm, which combined with the effective stress of lumbar vertebrae spongy bone calculated from FEM. Conclusions: The child-lifting motion could increase the risk of lumbar degeneration, fatigue, and injury in elderly women, and they should keep below the frequency limit of the motion of lifting children in their daily life. This study could put forward scientific injury prevention guidance to Chinese elderly women who lift children in daily life frequently.

Effects of non-supervised exercise interventions on bone mineral density in adult women: a systematic review and meta­analysis.

Osteoporosis is a major health issue worldwide. This study analyzes the effects of non-supervised osteoporosis prevention programs on bone mineral density. Non-supervised exercise increases femoral neck and lumbar spine bone mineral density in adult women. Thus, it might be effective for preventing or treating osteoporosis or osteopenia in this population. INTRODUCTION: Osteoporosis is a major health issue worldwide. Social distancing measures due to COVID-19 have hindered the chances to take part in supervised osteoporosis prevention exercise programs. The purpose of the present study is to systematically review and meta-analyze the effects of non-supervised osteoporosis prevention exercise programs on bone mineral density (BMD) in adult women. METHODS: A comprehensive search of electronic databases (n = 7) was conducted including (a) prospective randomized controlled trials (RCTs) comparing at least one exercise group vs. a control group with sedentary lifestyle or sham exercises; (b) baseline and follow-up BMD values, or BMD changes from baseline, at any skeletal site; (c) women over 30 years old; and (d) non-supervised exercise programs only. Subgroup analyses were performed for menopausal status, intervention duration, type of exercise, and osteopenia/osteoporosis status. RESULTS: Ten studies were included (n = 668). Random effect analyses showed that unsupervised exercise had beneficial effects on lumbar spine (LS) BMD with standardized mean difference (SMD) = 0.40 (95% confidence interval (CI): 0.03-0.77), and femoral neck (FN) BMD with SMD = 0.51 (95% CI: 0.16-0.85). Unsupervised exercise increased LS (SMD = 0.73 (95% CI: 0.13-1.33)) and FN BMD (SMD = 0.85 (95% CI: 0.33-1.37)) in women with osteopenia/osteoporosis, but not in healthy counterparts. CONCLUSION: Non-supervised exercise improves FN and LS BMD in adult women. Beneficial effects of exercise on FN and LS BMD might be more pronounced in those with poor bone health compared with healthy counterparts. More RCTs prescribing non-supervised, osteogenic exercise are required in this population. It is necessary to investigate the efficacy of remote/assistive technologies for delivering and monitoring non-supervised exercise interventions.

Outcome of COVID19 in Patients With Osteogenesis Imperfecta: A Retrospective Multicenter Study in Saudi Arabia.

Background: Although genetic diseases are rare, children with such conditions who get infected with COVID-19 tend to have a severe illness requiring hospitalization. Osteogenesis imperfecta (OI) is a rare genetic disorder of collagen resulting in fractures and skeletal deformities. Kyphoscoliosis, restrictive lung disease, and pneumonia worsen the prognosis of patients with OI. The use of bisphosphonate improves bone mineral density (BMD) and reduces fractures in OI. There is no literature describing the impact of COVID-19 in patients with OI. Methodology: A retrospective multi-center study was performed in three hospitals in Jeddah and Riyadh, Saudi Arabia, from March 1st, 2020, until August 31st, 2021, aiming to evaluate the outcome of COVID-19 in patients with OI. Demographics, vaccination status, underlying kyphoscoliosis, functional status, use of bisphosphonate, BMD, and COVID-19 severity, and course were recorded for all patients. Results: Twelve cases of confirmed COVID-19 were identified among 146 patients with OI. 9 (75%) of patients were less than 18 years, 6 (50%) were male, 5 (41%) had kyphoscoliosis, and 5 (41%) were wheelchair-bound. 6 (50%) received bisphosphonate, and 7(58%) had normal BMD. All patients had mild disease and did not require hospitalization. None of OI the patients with COVID-19 were fully vaccinated before the infection, and some were ineligible for vaccination. Conclusion: Patients with OI and COVID-19 in our study recovered without complications, unlike patients with other genetic diseases. Young age and mild illness contributed to the favorable outcome. Half of the patients received bisphosphonate and had normal BMD.

Consensus evidence-based clinical practice guidelines for the diagnosis and treat-to-target management of osteoporosis in Africa: an initiative by the African Society of Bone Health and Metabolic Bone Diseases.

The objective of this consensus statement is to inform the clinical practice communities, research centres and policymakers across Africa of the results of the recommendations for osteoporosis prevention, diagnosis and management. The developed guideline provides state-of-the-art information and presents the conclusions and recommendations of the consensus panel regarding these issues. PURPOSE: To reach an African expert consensus on a treat-to-target strategy, based on current evidence for best practice, for the management of osteoporosis and prevention of fractures. METHOD: A 3-round Delphi process was conducted with 17 osteoporosis experts from different African countries. All rounds were conducted online. In round 1, experts reviewed a list of 21 key clinical questions. In rounds 2 and 3, they rated the statements stratified under each domain for its fit (on a scale of 1-9). After each round, statements were retired, modified or added in view of the experts' suggestions and the percent agreement was calculated. Statements receiving rates of 7-9 by more than 75% of experts' votes were considered as achieving consensus. RESULTS: The developed guidelines adopted a fracture risk-centric approach. Results of round 1 revealed that of the 21 proposed domains, 10 were accepted whereas 11 were amended. In round 2, 32 statements were presented: 2 statements were retired for similarity, 9 statements reached consensus, whereas modifications were suggested for 21 statements. After the 3rd round of rating, the experts came to consensus on the 32 statements. Frequency of high-rate recommendation ranged from 83.33 to 100%. The response rate of the experts was 100%. An algorithm for the osteoporosis management osteoporosis was suggested. CONCLUSION: This study is an important step in setting up a standardised osteoporosis service across the continent. Building a single model that can be applied in standard practice across Africa will enable the clinicians to face the key challenges of managing osteoporosis; furthermore, it highlights the unmet needs for the policymakers responsible for providing bone health care together with and positive outcomes of patients' care.

Subtyping CKD Patients by Consensus Clustering: The Chronic Renal Insufficiency Cohort (CRIC) Study.

BACKGROUND: CKD is a heterogeneous condition with multiple underlying causes, risk factors, and outcomes. Subtyping CKD with multidimensional patient data holds the key to precision medicine. Consensus clustering may reveal CKD subgroups with different risk profiles of adverse outcomes. METHODS: We used unsupervised consensus clustering on 72 baseline characteristics among 2696 participants in the prospective Chronic Renal Insufficiency Cohort (CRIC) study to identify novel CKD subgroups that best represent the data pattern. Calculation of the standardized difference of each parameter used the cutoff of ±0.3 to show subgroup features. CKD subgroup associations were examined with the clinical end points of kidney failure, the composite outcome of cardiovascular diseases, and death. RESULTS: The algorithm revealed three unique CKD subgroups that best represented patients' baseline characteristics. Patients with relatively favorable levels of bone density and cardiac and kidney function markers, with lower prevalence of diabetes and obesity, and who used fewer medications formed cluster 1 (n=1203). Patients with higher prevalence of diabetes and obesity and who used more medications formed cluster 2 (n=1098). Patients with less favorable levels of bone mineral density, poor cardiac and kidney function markers, and inflammation delineated cluster 3 (n=395). These three subgroups, when linked with future clinical end points, were associated with different risks of CKD progression, cardiovascular disease, and death. Furthermore, patient heterogeneity among predefined subgroups with similar baseline kidney function emerged. CONCLUSIONS: Consensus clustering synthesized the patterns of baseline clinical and laboratory measures and revealed distinct CKD subgroups, which were associated with markedly different risks of important clinical outcomes. Further examination of patient subgroups and associated biomarkers may provide next steps toward precision medicine.

Effect of Calcium Fortified Foods on Health Outcomes: A Systematic Review and Meta-Analysis.

Calcium supplementation and fortification are strategies widely used to prevent adverse outcome in population with low-calcium intake which is highly frequent in low-income settings. We aimed to determine the effectiveness and cost-effectiveness of calcium fortified foods on calcium intake and related health, or economic outcomes. We performed a systematic review and meta-analysis involving participants of any age or gender, drawn from the general population. We searched PubMed, Agricola, EMBASE, CINAHL, Global Health, EconLit, the FAO website and Google until June 2019, without language restrictions. Pair of reviewers independently selected, extracted data and assessed the risk of bias of included studies using Covidence software. Disagreements were resolved by consensus. We performed meta-analyses using RevMan 5.4 and subgroup analyses by study design, age group, and fortification levels. We included 20 studies of which 15 were randomized controlled trials (RCTs), three were non-randomised studies and two were economic evaluations. Most RCTs had high risk of bias on randomization or blinding. Most represented groups were women and children from 1 to 72 months, most common intervention vehicles were milk and bakery products with a fortification levels between 96 and 1200 mg per 100 g of food. Calcium intake increased in the intervention groups between 460 mg (children) and 1200 mg (postmenopausal women). Most marked effects were seen in children. Compared to controls, height increased 0.83 cm (95% CI 0.00; 1.65), plasma parathyroid hormone decreased -1.51 pmol/L, (-2.37; -0.65), urine:calcium creatinine ratio decreased -0.05, (-0.07; -0.03), femoral neck and hip bone mineral density increased 0.02 g/cm2 (0.01; 0.04) and 0.03 g/cm2 (0.00; 0.06), respectively. The largest cost savings (43%) reported from calcium fortification programs came from prevented hip fractures in older women from Germany. Our study highlights that calcium fortification leads to a higher calcium intake, small benefits in children's height and bone health and also important evidence gaps for other outcomes and populations that could be solved with high quality experimental or quasi-experimental studies in relevant groups, especially as some evidence of calcium supplementation show controversial results on the bone health benefit on older adults.