Long-term trajectories of peak expiratory flow rate in older men and women show linear decline mainly determined by baseline levels.

BACKGROUND: Peak expiratory flow rate (PEFR) predicts mortality and other negative health outcomes. However, little evidence exists on how PEFR changes with ageing and how trajectories of change differ among older people. AIMS: To identify trajectories of PEFR in older men and women, and to study characteristics associated with these trajectories. METHODS: Data from the Longitudinal Aging Study Amsterdam were used, an ongoing cohort study in a representative sample of Dutch older men and women. PEFR was assessed using the Mini-Wright peak flow meter across a 13-year follow-up in 991 men and 1107 women. Trajectories were analyzed using Latent Class Growth Analysis. RESULTS: Mean age was 72.5 (SD 8.4) in men and 72.4 (SD 8.4) in women. In men, three declining trajectories were identified, i.e. high, intermediate and low, with prevalences of 30%, 46% and 24%, respectively. In women, two declining trajectories were identified, i.e. high and low, with prevalences of 62 and 38%. All trajectories showed linear decline and differed mostly with regard to their intercept. Significant differences between trajectories with regard to baseline demographic, health and lifestyle characteristics were observed, e.g., men and women in the low PEFR trajectory were older, had more chronic diseases, and were more often smoker. DISCUSSION AND CONCLUSIONS: Trajectories in both men and women differ mainly in baseline level of PEFR and not in rate of decline over time. Therefore, one PEFR measurement might be sufficient to give an indication of the trajectory that an older adult is likely to follow.

Bone loss and new vertebral fractures during treatment with romosozumab: a case-report.

PURPOSE: This study aimed to illustrate the possibility of an unfavorable response to treatment with the anabolic agent romosozumab for patients with severe osteoporosis and to discuss explanations for treatment failure. METHODS: Dual-energy x-ray absorptiometry (DXA) including vertebral fracture assessment (VFA) and X-rays of the thoracolumbar spine was used to assess bone mineral density (BMD) and the presence of vertebral fractures before and after treatment with romosozumab. RESULTS: Our patient developed a decrease in the BMD of the hip, two incident new vertebral fractures, and worsening of one prevalent vertebral fracture during 1 year treatment with romosozumab. We have not detected non-adherence, there was no pretreatment with anti-resorptives, and we observed no signs of secondary osteoporosis and/or comorbidities. CONCLUSION: As the number of patients treated with romosozumab is rising, it becomes more likely that more patients will be found with new fractures and/or an unfavorable BMD response. Probably, the unfavorable response is a (bad) chance finding, but we think it is crucial for clinicians and patients to exclude nonadherence, new comorbidities and pretreatment with anti-resorptives as explanation in these patients.

Methodological aspects of in vivo axial loading in rodents: a systematic review.

Axial loading in rodents provides a controlled setting for mechanical loading, because load and subsequent strain, frequency, number of cycles and rest insertion between cycles, are precisely defined. These methodological aspects as well as factors, such as ovariectomy, aging, and disuse may affect the outcome of the loading test, including bone mass, structure, and bone mineral density. This review aims to overview methodological aspects and modifying factors in axial loading on bone outcomes. A systematic literature search was performed in bibliographic databases until December 2021, which resulted in 2183 articles. A total of 144 articles were selected for this review: 23 rat studies, 74 mouse studies, and 47 knock out (KO) mouse studies. Results indicated that peak load, frequency, and number of loading cycles mainly affected the outcomes of bone mass, structure, and density in both rat and mouse studies. It is crucial to consider methodological parameters and modifying factors such as age, sex-steroid deficiency, and disuse in loading protocols for the prediction of loading-related bone outcomes.

Calcifediol: a review of its pharmacological characteristics and clinical use in correcting vitamin D deficiency.

BACKGROUND: In addition to the role of vitamin D in bone mineralization, calcium and phosphate homeostasis, and skeletal health, evidence suggests an association between vitamin D deficiency and a wide range of chronic conditions. This is of clinical concern given the substantial global prevalence of vitamin D deficiency. Vitamin D deficiency has traditionally been treated with vitamin D3 (cholecalciferol) or vitamin D2 (ergocalciferol). Calcifediol (25-hydroxyvitamin D3) has recently become available more widely. METHODS: By means of targeted literature searches of PubMed, this narrative review overviews the physiological functions and metabolic pathways of vitamin D, examines the differences between calcifediol and vitamin D3, and highlights clinical trials conducted with calcifediol in patients with bone disease or other conditions. RESULTS: For supplemental use in the healthy population, calcifediol can be used at doses of up to 10 µg per day for children ≥ 11 years and adults and up to 5 µg/day in children 3-10 years. For therapeutic use of calcifediol under medical supervision, the dose, frequency and duration of treatment is determined according to serum 25(OH)D concentrations, condition, type of patient and comorbidities. Calcifediol differs pharmacokinetically from vitamin D3 in several ways. It is independent of hepatic 25-hydroxylation and thus is one step closer in the metabolic pathway to active vitamin D. At comparable doses to vitamin D3, calcifediol achieves target serum 25(OH)D concentrations more rapidly and in contrast to vitamin D3, it has a predictable and linear dose-response curve irrespective of baseline serum 25(OH)D concentrations. The intestinal absorption of calcifediol is relatively preserved in patients with fat malabsorption and it is more hydrophilic than vitamin D3 and thus is less prone to sequestration in adipose tissue. CONCLUSION: Calcifediol is suitable for use in all patients with vitamin D deficiency and may be preferable to vitamin D3 for patients with obesity, liver disease, malabsorption and those who require a rapid increase in 25(OH)D concentrations.

[Increased fracture risk and fracture prevention]. / Verhoogd fractuurrisico en fractuurpreventie.

An increased fracture risk is a common chronic condition leading to a rising number of fractures, which are injurious to patients and costly to the health care system. Effective diagnostic and treatment options are available for primary and secondary prevention. In this article, we will answer specific practical questions with respect to increased fracture risk and fracture prevention. Topics discussed include definitions, risk factors, the diagnostic modalities and treatment options.

[Vitamin D supplementation not useful for all older people]. / Vitamine D niet zinvol voor alle 50-plussers.

An estimated 1.5 million Dutch people take vitamin D supplements on prescription, not including those who take multivitamins or vitamin D over the counter. Yet, controversial health benefits of vitamin D supplementation in the general population continues, often explained with not adequately powered studies, combination therapy with calcium, high bolus doses of vitamin D and poor study designs. Recently, the VITAL study does not show an effect in fracture incidence after treatment with daily vitamin D (2000IU) compared to placebo. However, zooming into the results a positive trend is observed in patients with a fragility fracture and/or using anti-osteoporosis medication. Additionally this study does not rule out a positive effect of vitamin D supplementation in severe vitamin D deficiency and high fracture risk patients.

Longitudinal Aging Study Amsterdam COVID-19 exposure index: a cross-sectional analysis of the impact of the pandemic on daily functioning of older adults.

OBJECTIVES: The aim of this study was to develop an index to measure older adults' exposure to the COVID-19 pandemic and to study its association with various domains of functioning. DESIGN: Cross-sectional study. SETTING: The Longitudinal Aging Study Amsterdam (LASA), a cohort study in the Netherlands. PARTICIPANTS: Community-dwelling older adults aged 62-102 years (n=1089) who participated in the LASA COVID-19 study (June-September 2020), just after the first wave of the pandemic. PRIMARY OUTCOME MEASURES: A 35-item COVID-19 exposure index with a score ranging between 0 and 1 was developed, including items that assess the extent to which the COVID-19 situation affected daily lives of older adults. Descriptive characteristics of the index were studied, stratified by several sociodemographic factors. Logistic regression analyses were performed to study associations between the exposure index and several indicators of functioning (functional limitations, anxiety, depression and loneliness). RESULTS: The mean COVID-19 exposure index score was 0.20 (SD 0.10). Scores were relatively high among women and in the southern region of the Netherlands. In models adjusted for sociodemographic factors and prepandemic functioning (2018-2019), those with scores in the highest tertile of the exposure index were more likely to report functional limitations (OR: 2.24; 95% CI: 1.48 to 3.38), anxiety symptoms (OR: 3.14; 95% CI: 1.82 to 5.44), depressive symptoms (OR: 2.49; 95% CI: 1.55 to 4.00) and loneliness (OR: 2.97; 95% CI: 2.08 to 4.26) than those in the lowest tertile. CONCLUSIONS: Among older adults in the Netherlands, higher exposure to the COVID-19 pandemic was associated with worse functioning in the physical, mental and social domain. The newly developed exposure index may be used to identify persons for whom targeted interventions are needed to maintain or improve functioning during the pandemic or postpandemic.

Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses.

BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

RANKL inhibition for giant cell lesions of the jaw: A retrospective cohort analysis.

BACKGROUND: In all giant-cell-rich lesions (GCRL) occurring in bone, a common underlying excessive RANKL expression is held responsible for the osteolytic activity. Apart from giant cell tumour of bone (GCTB), systematic outcome analysis of RANKL inhibition in other GCRL is unavailable. The aim of this study is to assess the efficacy and safety of a 1-year denosumab protocol in giant cell lesions of the jaw (GCLJ). METHODS: A retrospective cohort study was conducted compromising patients treated with a 1-year protocol of monthly subcutaneously administered 120 mg denosumab. Objective tumour response based on histology and imaging was used to calculate objective tumour response rate, progression-free survival (PFS) and time to progression. Type, severity and frequency of adverse events were recorded in a standardised way to assess safety. RESULTS: Twenty patients, predominantly female (90%), were included. Fifty-five per cent of lesions were located in the mandible; most classified as aggressive lesions (90%). Thirty-five per cent (7/20) of cases were either recurrent after prior treatment or progressive, while on other drug treatment. Objective tumour response rate was 100% after 12 months of treatment. Median PFS was 50.4 months (95% CI 38.0-62.8) with a cumulative PFS rate of 22.6% (95% CI 1.8-43.4) at 5 years follow-up. Median time to progression was 38.4 months (95% CI 26.0-50.8). Treatment was well tolerated, and none of the patients had to interrupt therapy for toxicity. CONCLUSION: High-dose denosumab is effective and safe in achieving a complete response in GCLJ within 12 months. The high long-term relapse rate after treatment cessation is the main obstacle for denosumab to become standard treatment for GCLJ.

Vitamin D supplementation in chronic obstructive pulmonary disease patients with low serum vitamin D: a randomized controlled trial.

BACKGROUND: Vitamin D deficiency is frequently found in patients with chronic obstructive pulmonary disease (COPD). Vitamin D has antimicrobial, anti-inflammatory, and immunomodulatory effects. Therefore, supplementation may prevent COPD exacerbations, particularly in deficient patients. OBJECTIVES: We aimed to assess the effect of vitamin D supplementation on exacerbation rate in vitamin D-deficient patients with COPD. METHODS: We performed a multicenter, double-blind, randomized controlled trial. COPD patients with ≥1 exacerbations in the preceding year and a vitamin D deficiency (15-50 nmol/L) were randomly allocated in a 1:1 ratio to receive either 16,800 International Units (IU) vitamin D3 or placebo once a week during 1 y. Primary outcome of the study was exacerbation rate. Secondary outcomes included time to first and second exacerbations, time to first and second hospitalizations, use of antibiotics and corticosteroids, pulmonary function, maximal respiratory mouth pressure, physical performance, skeletal muscle strength, systemic inflammatory markers, nasal microbiota composition, and quality of life. RESULTS: The intention-to-treat population consisted of 155 participants. Mean ± SD serum 25-hydroxyvitamin D [25(OH)D] concentration after 1 y was 112 ± 34 nmol/L in the vitamin D group, compared with 42 ± 17 nmol/L in the placebo group. Vitamin D supplementation did not affect exacerbation rate [incidence rate ratio (IRR): 0.90; 95% CI: 0.67, 1.21]. In a prespecified subgroup analysis in participants with 25(OH)D concentrations of 15-25 nmol/L (n = 31), no effect of vitamin D supplementation was found (IRR: 0.91; 95% CI: 0.43, 1.93). No relevant differences were found between the intervention and placebo groups in terms of secondary outcomes. CONCLUSIONS: Vitamin D supplementation did not reduce exacerbation rate in COPD patients with a vitamin D deficiency.This trial was registered at clinicaltrials.gov as NCT02122627.

Trends in Vitamin D Status Around the World.

Vitamin D status varies across all continents and countries. Vitamin D status usually is adequate in Latin America and Australia, but in contrast it is very low in the Middle East and some countries in Asia. Trends in vitamin D status, whether it improves or declines over the years, carry important messages. Trends usually are small, but can be predictors and indicators of general health. Vitamin D status has improved in the older population in the United States, and improvement relates to dairy use and vitamin D supplements. To the contrary, vitamin D status has declined in the Inuit population of Canada due to a change from a traditional fish diet to a Western diet. A large improvement was seen in Finland after mandatory fortification of dairy products was introduced. Determinants of decline are less sun exposure, increased use of sunscreen, increase of body mass index (BMI), less physical activity, and poor socioeconomic status. Determinants of increase are food fortification with vitamin D and vitamin D supplements. Food fortification can lead to a population-wide increase in vitamin D status as shown by the Finnish example. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Association of Thyroid Dysfunction With Cognitive Function: An Individual Participant Data Analysis.

Importance: In clinical guidelines, overt and subclinical thyroid dysfunction are mentioned as causal and treatable factors for cognitive decline. However, the scientific literature on these associations shows inconsistent findings. Objective: To assess cross-sectional and longitudinal associations of baseline thyroid dysfunction with cognitive function and dementia. Design, Setting, and Participants: This multicohort individual participant data analysis assessed 114 267 person-years (median, 1.7-11.3 years) of follow-up for cognitive function and 525 222 person-years (median, 3.8-15.3 years) for dementia between 1989 and 2017. Analyses on cognitive function included 21 cohorts comprising 38 144 participants. Analyses on dementia included eight cohorts with a total of 2033 cases with dementia and 44 573 controls. Data analysis was performed from December 2016 to January 2021. Exposures: Thyroid function was classified as overt hyperthyroidism, subclinical hyperthyroidism, euthyroidism, subclinical hypothyroidism, and overt hypothyroidism based on uniform thyrotropin cutoff values and study-specific free thyroxine values. Main Outcomes and Measures: The primary outcome was global cognitive function, mostly measured using the Mini-Mental State Examination. Executive function, memory, and dementia were secondary outcomes. Analyses were first performed at study level using multivariable linear regression and multivariable Cox regression, respectively. The studies were combined with restricted maximum likelihood meta-analysis. To overcome the use of different scales, results were transformed to standardized mean differences. For incident dementia, hazard ratios were calculated. Results: Among 74 565 total participants, 66 567 (89.3%) participants had normal thyroid function, 577 (0.8%) had overt hyperthyroidism, 2557 (3.4%) had subclinical hyperthyroidism, 4167 (5.6%) had subclinical hypothyroidism, and 697 (0.9%) had overt hypothyroidism. The study-specific median age at baseline varied from 57 to 93 years; 42 847 (57.5%) participants were women. Thyroid dysfunction was not associated with global cognitive function; the largest differences were observed between overt hypothyroidism and euthyroidism-cross-sectionally (-0.06 standardized mean difference in score; 95% CI, -0.20 to 0.08; P = .40) and longitudinally (0.11 standardized mean difference higher decline per year; 95% CI, -0.01 to 0.23; P = .09). No consistent associations were observed between thyroid dysfunction and executive function, memory, or risk of dementia. Conclusions and Relevance: In this individual participant data analysis of more than 74 000 adults, subclinical hypothyroidism and hyperthyroidism were not associated with cognitive function, cognitive decline, or incident dementia. No rigorous conclusions can be drawn regarding the role of overt thyroid dysfunction in risk of dementia. These findings do not support the practice of screening for subclinical thyroid dysfunction in the context of cognitive decline in older adults as recommended in current guidelines.

Older adults report cancellation or avoidance of medical care during the COVID-19 pandemic: results from the Longitudinal Aging Study Amsterdam.

PURPOSE: Delay of routine medical care during the COVID-19 pandemic may have serious consequences for the health and functioning of older adults. The aim of this study was to investigate whether older adults reported cancellation or avoidance of medical care during the first months of the COVID-19 pandemic, and to explore associations with health and socio-demographic characteristics. METHODS: Cross-sectional data of 880 older adults aged ≥ 62 years (mean age 73.4 years, 50.3% female) were used from the COVID-19 questionnaire of the Longitudinal Aging Study Amsterdam, a cohort study among community-dwelling older adults in the Netherlands. Cancellation and avoidance of care were assessed by self-report, and covered questions on cancellation of primary care (general practitioner), cancellation of hospital outpatient care, and postponed help-seeking. Respondent characteristics included age, sex, educational level, loneliness, depression, anxiety, frailty, multimorbidity and information on quarantine. RESULTS: 35% of the sample reported cancellations due to the COVID-19 situation, either initiated by the respondent (12%) or by healthcare professionals (29%). Postponed help-seeking was reported by 8% of the sample. Multimorbidity was associated with healthcare-initiated cancellations (primary care OR = 1.92, 95% CI = 1.09-3.50; hospital OR = 1.86, 95% CI = 1.28-2.74) and respondent-initiated hospital outpatient cancellations (OR = 2.02, 95% CI = 1.04-4.12). Depressive symptoms were associated with postponed help-seeking (OR = 1.15, 95% CI = 1.06-1.24). CONCLUSION: About one third of the study sample reported cancellation or avoidance of medical care during the first months of the pandemic, and this was more common among those with multiple chronic conditions. How this impacts outcomes in the long term should be investigated in future research.

[Osteoporosis and increased risk of fractures]. / Osteoporose en verhoogd fractuurrisico.

Osteoporosis is a common condition in older people. This condition leads to increased risk of fractures and is associated with morbidity and mortality. The number of patients with osteoporosis will increase significantly in the years to come due to the increasing numbers of older people and increasing life expectancy. This will be accompanied by increasing demand for care and clinical practice will be faced with questions about therapeutic options and the optimal treatment duration for patients with osteoporosis or increased risk of fractures. In this educational article, we are using practical questions to provide an overview of pathophysiology, diagnostics and treatment of osteoporosis and increased risk of fractures.

Short-Term Glucocorticoid Treatment Reduces Circulating Sclerostin Concentrations in Healthy Young Men: A Randomized, Placebo-Controlled, Double-Blind Study.

Glucocorticoid use is the most common cause of osteoporosis in young individuals. In the current study, we investigated the effects of glucocorticoid treatment on circulating sclerostin concentrations and serum bone turnover markers in healthy young men. We performed additional measurements in two combined randomized, placebo-controlled, double-blind, dose-response intervention studies: 64 healthy men (age: 22 ± 2 years; BMI: 22.1 ± 1.7 kg/m2) were allocated to receive placebo (n = 16), prednisolone 7.5 mg once daily (n = 24), or prednisolone 30 mg once daily (n = 24) for 2 weeks using block randomization. Primary outcome variables were serum sclerostin and serum bone turnover markers (CTx and P1NP), before and after the intervention. Baseline characteristics and variables did not differ between intervention groups. Compared with placebo, prednisolone high-dose decreased serum sclerostin concentrations (-8.5 [-28.0 to 7.3] versus 1.5 [-6.5 to 20.0] pg/mL, p = 0.048), decreased P1NP concentrations (-28.0 [-39.3 to -18.3] versus -1.5 [-15.3 to 11.3] µg/L, p < 0.001) and increased CTx concentrations (108.0 [55.0 to 177.0] versus 64.0 [-24.3 to 120.0] ng/L, p = 0.038). Compared with placebo, prednisolone low-dose did not alter sclerostin concentrations (p = 0.5) or CTx concentrations (p = 0.7), but tended to decrease P1NP concentrations (-9.0 [-24.0 to -1.3] versus -1.5 [-15.3 to 11.3] µg/L, p = 0.095). At baseline concentrations of sclerostin were positively correlated with concentrations of CTx (Spearman's rank correlation coefficient ρ = +0.409, p = 0.001), but not with P1NP. No significant correlations were observed between changes in outcome variables during the interventions. Short-term high-dose, but not low-dose, prednisolone treatment reduces serum sclerostin concentrations in healthy young men. Whether this reflects a counter regulatory mechanism to compensate glucocorticoid-induced negative effects through other mechanisms remains to be elucidated. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Adiposity is a confounding factor which largely explains the association of serum vitamin D concentrations with C-reactive protein, leptin and adiponectin.

OBJECTIVE: The role of adiposity in the relationship between vitamin D and inflammation is unknown. Our aim was therefore to assess the association of serum 25-hydroxyvitamin D (25(OH)D) with C-reactive protein (CRP), leptin and adiponectin and the role of adiposity in this relationship. METHODS: This is a cross-sectional analysis of The Netherlands Epidemiology of Obesity Study (NEO), a population-based cohort study in men and women aged 45 to 65 years. Main outcome measures were CRP, leptin and adiponectin. In the linear regression analyses we adjusted for age, sex, ethnicity, creatinine, education, alcohol use, smoking status, physical activity, number of chronic diseases, season, total body fat and waist circumference. RESULTS: Of the 6287 participants, 21% were vitamin D deficient (serum 25(OH)D < 50 nmol/L). Mean (SD) age and BMI were 56 (6) years and 26.3 (4.4) kg/m2, respectively. Although after adjustment for most examined potential confounders, each 10 nmol/L increase in serum 25(OH)D was associated with 2.3% (95%CI: -4.0 to -0.5) lower CRP, 3.5% (-4.7 to -2.2) lower leptin, and 0.13 ng/mL (0.04-0.21) higher adiponectin, most of these associations seemed to largely stem from an additional potential confounder - adiposity - as they either disappeared (leptin and CRP) or were largely diminished (adiponectin) upon further adjustment for adiposity indices (total body fat and waist circumference). CONCLUSION: We found that measures of adiposity largely explained the negative association of serum 25(OH)D with the pro-inflammatory CRP and leptin, and the positive association with the anti-inflammatory adiponectin. These results suggest that future studies should take the effect of adiposity into account.

Oxidation of parathyroid hormone.

Parathyroid hormone (PTH) is the key hormone regulating calcium homeostasis and, as such, is an important diagnostic and prognostic marker. Although the measurement of PTH has greatly improved over the past few decades, oxidation status thereof is unaccounted for in currently used assays. PTH can be oxidized on methionine residues located at amino acid positions 8 and 18. This is a relevant post-translational modification as, due to refolding of the molecule, it results in the decreased ability to activate the PTH1 receptor. Although this loss of activity after oxidation was observed as early as 1934, only recently a method was developed to measure and distinguish non-oxidized PTH (n-oxPTH) from oxidized PTH. This method creates exciting possibilities for studying more specifically the role of n-oxPTH in physiology and pathology. Therefore, it can now be explored what the clinical implications of measuring n-oxPTH will be. Herein, we review the available evidence of the effect of oxidation on the biological activity of PTH. We also discuss studies examining the mechanism of PTH oxidation in vivo and efforts to stabilize synthetic PTH ex vivo for therapeutic applications. Lastly, the available studies regarding the clinical significance of n-oxPTH are evaluated and future directions discussed.

Fracture Risk in Trans Women and Trans Men Using Long-Term Gender-Affirming Hormonal Treatment: A Nationwide Cohort Study.

Concerns about bone health in transgender people using gender-affirming hormonal treatment (HT) exist, but the fracture risk is not known. In this nationwide cohort study, we aimed to compare the fracture incidence in transgender people using long-term HT with an age-matched reference population. All adult transgender people who started HT before 2016 at our gender-identity clinic were included and were linked to a random population-based sample of 5 age-matched reference men and 5 age-matched reference women per person. Fracture incidence was determined using diagnoses from visits to hospital emergency rooms nationwide between 2013 and 2015. A total of 1089 trans women aged <50 years (mean 38 ± 9 years) and 934 trans women aged ≥50 years (mean 60 ± 8 years) using HT for median 8 (interquartile range [IQR] 3-16) and 19 (IQR 11-29) years, respectively, were included. A total of 2.4% of the trans women aged <50 years had a fracture, whereas 3.0% of the age-matched reference men (odds ratio [OR] = 0.78, 95% confidence interval [CI] 0.51-1.19) and 1.6% of the age-matched reference women (OR = 1.49, 95% CI 0.96-2.32) experienced a fracture. In trans women aged ≥50 years, 4.4% experienced a fracture compared with 2.4% of the age-matched reference men (OR = 1.90, 95% CI 1.32-2.74) and 4.2% of the age-matched reference women (OR = 1.05, 95% CI 0.75-1.49). A total of 1036 trans men (40 ± 14 years) using HT for median 9 (IQR 2-22) years were included. Fractures occurred in 1.7% of the trans men, 3.0% of the age-matched reference men (OR = 0.57, 95% CI 0.35-0.94), and 2.2% of the age-matched reference women (OR = 0.79, 95% CI 0.48-1.30). In conclusion, fracture risk was higher in older trans women compared with age-matched reference men. In young trans women, fracture risk tended to be increased compared with age-matched reference women. Fracture risk was not increased in young trans men. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Bone geometry and trabecular bone score in transgender people before and after short- and long-term hormonal treatment.

BACKGROUND: Gender-affirming hormonal treatment (HT) in adult transgender people influences bone mineral density (BMD). Besides BMD, bone geometry and trabecular bone score are associated with fracture risk. However, it is not known whether bone geometry and TBS changes during HT. PURPOSE: To investigate the bone geometry and TBS in adult transgender people at different time points, up to 25 years, of HT. METHODS: A total of 535 trans women and 473 trans men were included, who were divided into three groups at time of their DXA: 20-29 years, 30-39 years, and 40-59 years. Subsequently, each group was divided into different HT durations: baseline, or after 5, 15, or 25 years of HT. Hip structure analysis was performed to measure subperiosteal width, endocortical diameter, average cortical thickness, and section modulus. TBS was calculated based on lumbar spine DXA images. RESULTS: In trans women in all age groups and in young trans men, no differences were observed in periosteal width, endocortical diameter, average cortical thickness, and section modulus for different durations of HT. In trans men aged 40-59 years, subperiosteal width, endocortical diameter, and section modulus were slightly higher in the groups who were using HT compared to the (peri- or postmenopausal) baseline group. In younger trans women, TBS tended to be higher in those using HT compared to the baseline groups, and in older trans women TBS was higher in those using HT for 25 years versus baseline (+0.04, 95%CI +0.00; +0.08). In younger trans men, TBS tended to be lower in those who used HT compared to the baseline groups, and in older trans men TBS was lower in those using 5 years HT versus baseline (-0.05, 95%CI -0.08; -0.01). CONCLUSION: No differences in cortical bone geometry parameters were found during different HT-durations. TBS increased in trans women and decreased in trans men, indicating that estrogens have positive effects on TBS. These data may be helpful in determining what sex reference values for calculating T-scores and Z-scores in adult transgender people should be used.