Lessons Learned: Evaluation of Fracture Liaison Service Quality Improvement Efforts in a Large Academic Healthcare System.

BACKGROUND: The Fracture Liaison Service (FLS) care model, a care coordination program for patients experiencing a fragility fracture, is proven to improve management of patients with an osteoporotic fracture, but treatment initiation gaps persist. OBJECTIVE: We describe the evolution of a centralized FLS within a university-based healthcare system, including impact of adding clinical pharmacist consultation, and describe circumstances surrounding continued care gaps. DESIGN: Cohort analysis of osteoporosis medication initiation before FLS, after initial implementation, and after addition of pharmacist consultation. PATIENTS: Individuals aged 65 and older experiencing any fragility fracture between 7/1/16 and 3/31/22. INTERVENTION: A centralized team outreached eligible patients, ordered dual x-ray absorptiometry and laboratory tests as needed, and scheduled an osteoporosis-focused primary care appointment. Three years after FLS implementation, clinical pharmacist consultative review was added prior to the primary care visit. MAIN MEASURES: Initiation of osteoporosis pharmacologic therapy, completion of DXA, primary care follow-up rate, and description of circumstances where therapy was not initiated. KEY RESULTS: Of 1204 new fractures between 7/1/16 and 3/31/22, 315 patients were enrolled in one of two FLS phases, and 89 eligible historical controls were identified. Medication initiation rates went from 22/89 (25%) pre-FLS to 201/428 (47%) after-FLS phase 1 [POST1] (p<0.001) and to 106/187 (57%) after FLS phase 2 (POST2), when clinical pharmacist consultation was added (p=0.03 versus POST1). DXA was completed in 56/89 (67%) of pre-FLS patients, 364/428 (85%) POST1 patients (p<0.001 versus pre), and 163/187 (87%) POST2 (p< 0.001 versus PRE, p=0.59 versus POST1). Of 375 patients who did not initiate osteoporosis medication, more in the combined post-FLS cohorts attended a follow-up primary care appointment (233/308, 76% attended, versus pre-FLS 41/67, 61%, p=0.016). CONCLUSION: An FLS including centralized outreach and care coordination significantly improved patient follow-up, DXA, and medication initiation. Addition of de-centralized pharmacist consultation further improved medication initiation rates.

Serum cortisol level to screen for significant hypothalamic-pituitary-adrenal axis suppression in patients receiving multiple steroid injections.

BACKGROUND: Morning serum cortisol level (mSCL) is a practical screening tool for hypothalamic-pituitary-adrenal (HPA) axis suppression and has been used to assess for duration of cortisol deficiency after epidural and peripheral glucocorticoid injections. More evidence is needed to establish the utility of mSCL in patients undergoing repeat injections with increasing cumulative glucocorticoid equivalent dose (CGED) that could place them at higher risk of HPA axis suppression. OBJECTIVES: To estimate the prevalence of spine injection candidates with significant HPA axis suppression (sigAS), to understand the correlation between 12 months of CGED and the presence of sigAS based on the timing of mSCL collection after the most recent glucocorticoid injection (within 6 weeks or between 6 weeks and 12 months), and to investigate demographic and clinical factors relating to sigAS. METHODS: Retrospective chart review of patients scheduled for spine injection who had an associated mSCL and documented histories of prior glucocorticoid injections. The steroid name, dose, type, and procedure location were recorded for each injection that occurred within 12 months before mSCL. CGED was calculated from standard glucocorticoid equivalent conversion factors. RESULTS: SigAS was present in 7.8% to 22% of the analysis cohorts. There was no association found between CGED and sigAS regardless of timing of mSCL. There was a trend toward lower mSCL and sigAS with increasing CGED. There were no significant relationships found between sigAS and overall demographic or clinical factors. CONCLUSIONS: A 3-fold reduction in the rate of sigAS was noted 6 weeks after the most recent steroid injection. Using mSCL provides a template to investigate the impact of CGED and the best timing for mSCL collection in order to define a more practical guideline to identify patients at higher risk of sigAS earlier and plan for future spine injections.

The Use of Injectable Estradiol in Transgender and Gender Diverse Adults: A Scoping Review of Dose and Serum Estradiol Levels.

OBJECTIVE: Feminizing gender-affirming hormone therapy is the mainstay of treatment for many transgender and gender diverse people. Injectable estradiol preparations are recommended by the World Professional Association for Transgender Health Standards of Care 8 and the Endocrine Society guidelines. Many patients prefer this route of administration, but few studies have rigorously assessed optimal dosing or route. METHODS: We performed a scoping review of the available data on estradiol levels achieved with various dosages of estradiol injections in transgender and gender diverse adults on feminizing gender-affirming hormone therapy. We also report on testosterone suppression, route (ie, subcutaneous vs intramuscular), and type of injectable estradiol ester as well as timing of blood draw relative to the most recent dose, where available. RESULTS: The data we reviewed suggest that the current guidelines, which recommend starting doses 2 to 10 mg weekly or 5 to 30 mg every 2 weeks of estradiol cypionate or valerate, are too high and likely lead to patients having supraphysiologic levels across much of their injection cycle. CONCLUSIONS: The optimal starting dose for injectable estradiol remains unclear and whether it should differ for cypionate and valerate. Based on the data available, we suggest that clinicians start injectable estradiol cypionate or valerate via subcutaneous or intramuscular injections at a dose ≤5 mg weekly and then titrate accordingly to keep levels within guideline-recommended range. Future studies should assess timing of injections and subsequent levels more precisely across the injection cycle and between esters.

ECHO "Bootcamp": An Innovative Training Model to Onboard Providers in the Care of Gender Diverse Patients.

Purpose: Extension for Community Health Outcomes (ECHO) is a model of continuing medical education meant to connect academic medical center-based specialists with community providers to increase capacity in managing complex health conditions. The purpose of this study was to evaluate the effectiveness of a shortened "bootcamp" ECHO model in increasing participant competence with topics related to transgender and gender diverse (TGD) health care and the impact of "bootcamp" participation on enrollment in an ongoing ECHO series. Methods: An ongoing monthly ECHO series was instituted on topics of TGD health. After 2 years, the team implemented a four-session "bootcamp" for four consecutive weeks during March 2022 to introduce foundational topics for new participants who had joined or were considering joining the ongoing series. Qualitative and quantitative results were collected from self-reported pre-/post-surveys as well as from in-session quizzes. Results: There were 71 participants in the "bootcamp" including health care providers and support staff. Attendees reported a 10.3% increase (p = 0.02) in self-reported comfort providing care to transgender patients. Pre-/post-knowledge improved in areas of health inequities (50% vs. 74% correct pre/post), surgical requirements (33% vs. 74%), and effects of masculinizing (55% vs. 70%) and feminizing (64% vs. 89%) hormone therapy. Prescribing providers reported a significant change across four areas of practice competency. Among 71 "bootcamp" participants, 15 registered for the ongoing program. Conclusion: Use of a "bootcamp" highlights ways to increase participant comfort and knowledge in providing TGD health care in a shortened timeframe and recruit new participants to an ongoing ECHO curriculum.

Proceedings of the 2021 Santa Fe Bone Symposium: Advances in the Management of Osteoporosis and Metabolic Bone Diseases.

The 2021 Virtual Santa Fe Bone Symposium was held August 5-8, with over 300 registered attendees from throughout the USA, and at least 18 other countries. This annual meeting focuses on applying advances in basic science and clinical research to the care of patients with osteoporosis and those with inherited and acquired disorders of bone metabolism. Participants represented a broad range of medical disciplines with an interest in skeletal diseases. These included physicians of many specialties and practice settings, fellows, advanced practice providers, fracture liaison service (FLS) coordinators, clinical researchers, and bone density technologists. There were lectures, case presentations, and panel discussions, all followed by interactive discussions. Breakout sessions included an FLS workshop, Bone Health TeleECHO workshop, special interest groups, meet-and-greet the faculty, and satellite symposia. The agenda covered topics of interest such as strategies for the use of osteoanabolic therapy, prevention of periprosthetic fractures, management of atypical femur fractures, what we know and don't know about vitamin D, advances in the use of dual-energy X-ray absorptiometry in the assessment of skeletal health, controversies and conundrums in osteoporosis care, skeletal health in transgender patients, management of patients with hypophosphatasia and hypophosphatemia, and treat-to-target approaches for managing patients with osteoporosis. The Proceedings of the 2021 Virtual Santa Fe Bone Symposium consists of highlights of each presentation with current strategies for optimizing the care of patients with skeletal disorders.

Routine Screening for Transgender and Gender Diverse Adults Taking Gender-Affirming Hormone Therapy: a Narrative Review.

Despite the growing number of adult transgender and gender diverse (TGD) patients seeking health services, there are many unknowns regarding how routine screening recommendations should be applied to TGD persons receiving gender-affirming hormone therapy (GAHT). Patients taking GAHT may have disease risks that differ from what is expected based on their sex assigned at birth or affirmed gender identity. We discuss two patient cases, one transgender man and one transgender woman who present for routine medical care, to review several conditions that may be impacted by the hormones utilized in masculinizing and feminizing GAHT and for which screening recommendations are available for TGD adults: cardiovascular risk factors, osteoporosis, breast cancer, cervical cancer, and prostate cancer. We reviewed the TGD-specific screening recommendations from several major medical organizations and programs and found them to be largely based upon expert opinion due to a lack of evidence. The goal of this narrative review is to assist healthcare professionals in counseling and screening their TGD patients when and where appropriate. Not all TGD adults have the ability or need to receive routine medical care from a specialized TGD health clinic; therefore, it is essential for all healthcare professionals involved in routine and gender-affirming care to have knowledge about these conditions and screenings.

Bone mineral density and estimated hip strength in men with anorexia nervosa, atypical anorexia nervosa and avoidant/restrictive food intake disorder.

OBJECTIVE: Few bone mineral density (BMD) data are available in men with anorexia nervosa (AN), and none in those with atypical AN (ATYP) (AN psychological symptoms without low weight) or avoidant/restrictive food intake disorder (ARFID) (restrictive eating without AN psychological symptoms). We investigated the prevalence and determinants of low BMD and estimated hip strength in men with these disorders. DESIGN: Cross-sectional: two centres. PATIENTS: A total of 103 men, 18-63 years: AN (n = 26), ARFID (n = 11), ATYP (n = 18), healthy controls (HC) (n = 48). MEASUREMENTS: Body composition, BMD and estimated hip strength (section modulus and buckling ratio) by DXA (Hologic). Serum 25OH vitamin D was quantified, as was daily calcium intake in a subset of subjects. RESULTS: Mean BMI was lowest in AN and ARFID, higher in ATYP and highest in HC (AN 14.7 ± 1.8, ARFID 15.3 ± 1.5, ATYP 20.6 ± 2.0, HC 23.7 ± 3.3 kg/m2 ) (P < 0.0005). Mean BMD Z-scores at spine and hip were lower in AN and ARFID, but not ATYP, than HC (postero-anterior (PA) spine AN -2.05 ± 1.58, ARFID -1.33 ± 1.21, ATYP -0.59 ± 1.77, HC -0.12 ± 1.17) (P < 0.05). 65% AN, 18% ARFID, 33% ATYP and 6% HC had BMD Z-scores <-2 at ≥1 site (AN and ATYP vs HC, P < 0.01). Mean section modulus Z-scores were lower in AN than HC (P < 0.01). Lower BMI, muscle mass and vitamin D levels (R = 0.33-0.64), as well as longer disease duration (R = -0.51 to -0.58), were associated with lower BMD (P < 0.05). CONCLUSIONS: Men with AN, ARFID and ATYP are at risk for low BMD. Men with these eating disorders who are low weight, or who have low muscle mass, long illness duration and/or vitamin D deficiency, may be at particularly high risk.

Bone Health in the Transgender Population.

It is well known that sex steroids, particularly estrogen, play a crucial role in the attainment and maintenance of peak bone density in all people. Transgender (trans) women have been frequently observed to have low bone density prior to initiation of gender-affirming hormone therapy, while trans men generally do not. With pharmacologic estrogen, many studies show improving bone density in trans women. With pharmacologic testosterone, bone density in trans men remains largely unchanged although androgens have indirect effects on bone health via changes in fat and lean mass. Much remains unknown about best practices to optimize bone health, interpret DXA scans and assess fracture risk in trans adults.

Bone density testing: science, the media, and patient care.

Dual-energy X-ray absorptiometry (DXA) is an inexpensive, noninvasive, widely available method for diagnosing osteoporosis, assessing fracture risk, and monitoring the effects of therapy. By diagnosing high-risk patients before a fracture occurs, clinicians can intervene early to reduce fracture risk. Appropriate use of DXA results in money saving for healthcare systems that might otherwise be spent for fracture-related care. Recent reports of studies evaluating DXA screening criteria and intervals for retesting have received considerable media coverage, sometimes suggesting that DXA is expensive, over-utilized, and unnecessary. This may lead to more patients who might benefit from early detection of osteoporosis remaining undiagnosed. We advocate for the use of current clinical practice guidelines with individualization of patient care factors to determine the optimal intervals for DXA testing.

Patients with nontuberculous mycobacterial lung disease exhibit unique body and immune phenotypes.

RATIONALE: Among patients with nontuberculous mycobacterial lung disease is a subset of previously healthy women with a slender body morphotype, often with scoliosis and/or pectus excavatum. We hypothesize that unidentified factors predispose these individuals to pulmonary nontuberculous mycobacterial disease. OBJECTIVES: To compare body morphotype, serum adipokine levels, and whole-blood cytokine responses of patients with pulmonary nontuberculous mycobacteria (pNTM) with contemporary control subjects who are well matched demographically. METHODS: We enrolled 103 patients with pNTM and 101 uninfected control subjects of similar demographics. Body mass index and body fat were quantified. All patients with pNTM and a subset of control subjects were evaluated for scoliosis and pectus excavatum. Serum leptin and adiponectin were measured. Specific cytokines important to host-defense against mycobacteria were measured in whole blood before and after stimulation. MEASUREMENTS AND MAIN RESULTS: Patients with pNTM and control subjects were well matched for age, gender, and race. Patients with pNTM had significantly lower body mass index and body fat and were significantly taller than control subjects. Scoliosis and pectus excavatum were significantly more prevalent in patients with pNTM. The normal relationships between the adipokines and body fat were lost in the patients with pNTM, a novel finding. IFN-γ and IL-10 levels were significantly suppressed in stimulated whole blood of patients with pNTM. CONCLUSIONS: This is the first study to comprehensively compare body morphotype, adipokines, and cytokine responses between patients with NTM lung disease and demographically matched controls. Our findings suggest a novel, predisposing immunophenotype that should be mechanistically defined.

Approach to the Patient: Hormonal Therapy in Transgender Adults With Complex Medical Histories.

While endocrinologists continue to initiate gender-affirming hormone therapy (GAHT) in healthy transgender and gender diverse (TGD) patients, they may also encounter more TGD patients in their clinics with complex medical histories that influence the patient-provider shared decision-making process for initiating or continuing GAHT. The purpose of this Approach to the Patient article is to describe management considerations in 2 adults with thromboembolic disease and 2 adults with low bone mineral density in the setting of feminizing and masculinizing GAHT.

Bone Density in Transgender Youth on Gender-Affirming Hormone Therapy.

Some transgender youth are treated with gonadotropin-releasing hormone agonists (GnRHa) followed by testosterone or estradiol, which may impact bone mineral density (BMD). This cross-sectional study of transgender youth (n = 56, aged 10.4-19.8 years, 53% assigned female at birth [AFAB]) utilized total body dual-energy x-ray absorptiometry to evaluate BMD Z-scores, and associations between GnRHa duration, body mass index (BMI), and BMD. Participants on GnRHa alone (n = 19, 14 assigned male at birth [AMAB], 5 AFAB) at the time of the study visit were 13.8 [12.8, 15.3] (median [IQR]) years old, had been on GnRHa for 10 [5.5, 19.5] months, and began GnRHa at age 12 [10.4, 12.6] years. Total body BMD Z-score for individuals on GnRHa monotherapy was -0.10 [-0.8, 0.4] (AFAB, female norms) and -0.65 [-1.4, 0.22] (AMAB, male norms). AFAB participants (n = 21) on testosterone were age 16.7 [15.9, 17.8] years, had been on testosterone for 11 [7.3, 14.5] months, and started testosterone at age 16 [14.8, 16.8] years; total body BMD Z-score -0.2 [-0.5, 0] (male norms) and 0.4 [-0.2, 0.7] (female norms). AMAB participants (n = 16) were age 16.2 [15.1, 17.4] years, had been on estradiol for 11 [5.6, 13.7] months, and started estradiol at age 16 [14.4, 16.7] years; total body BMD Z-score -0.4 [-1.1, 0.3] (male norms) and -0.2 [-0.7, 0.6] (female norms). BMD Z-score was negatively correlated with GnRHa duration (male norms: r = -0.5, P = .005; female norms: r = -0.4, P = .029) and positively correlated with BMI (male norms: r = 0.4, P = .003; female norms: r = 0.4, P = .004). In this cross-sectional cohort, total body BMD Z-scores were slightly below average, but lowest in the AMAB group on GnRHa monotherapy.

The association of gender-affirming hormone therapy duration and body mass index on bone mineral density in gender diverse adults.

Introduction: Feminizing and masculinizing gender-affirming hormone therapy (fGAHT, mGAHT) results in bone mineral density (BMD) maintenance or improvement over time in transgender and gender diverse (TGD) adults. Mostly European TGD studies have explored GAHT's impact on BMD, but the association of BMI and BMD in TGD adults deserves further study. Objective: To determine whether GAHT duration or BMI are associated with BMD and Z-scores among TGD young adults. Methods: Cross-sectional study of nonsmoking TGD adults aged 18-40 years without prior gonadectomy or gonadotropin-releasing hormone agonist (GnRHa) therapy taking GAHT for > 1 year. BMD and Z-scores were collected from dual-energy x-ray absorptiometry. Associations between femoral neck, total hip, and lumbar spine BMDs and Z-scores and the predictors, GAHT duration and BMI, were estimated using linear regression. Results: Among 15 fGAHT and 15 mGAHT, mean BMIs were 27.6 +/- standard deviation (SD) 6.4 kg/m2 and 25.3 +/- 5.9 kg/m2, respectively. Both groups had mean BMDs and Z-scores within expected male and female reference ranges at all three sites. Higher BMI among mGAHT was associated with higher femoral neck and total hip BMDs (femoral neck: ß = 0.019 +/- standard error [SE] 0.007 g/cm2, total hip: ß = 0.017 +/- 0.006 g/cm2; both p < 0.05) and Z-scores using male and female references. GAHT duration was not associated with BMDs or Z-scores for either group. Conclusions: Z-scores in young, nonsmoking TGD adults taking GAHT for > 1 year, without prior gonadectomy or GnRHa, and with mean BMIs in the overweight range, were reassuringly within the expected ranges for age based on male and female references. Higher BMI, but not longer GAHT duration, was associated with higher femoral neck and total hip BMDs and Z-scores among mGAHT. Larger, prospective studies are needed to understand how body composition changes, normal or low BMIs, and gonadectomy affect bone density in TGD adults.

Symptomatic reduction in free testosterone levels secondary to crizotinib use in male cancer patients.

BACKGROUND: Crizotinib is a tyrosine kinase inhibitor active against ALK, MET, and ROS1. We previously reported that crizotinib decreases testosterone in male patients. The detailed etiology of the effect, its symptomatic significance, and the effectiveness of subsequent testosterone replacement have not been previously reported. METHODS: Male cancer patients treated with crizotinib had total testosterone levels measured and results compared with non-crizotinib-treated patients. Albumin, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), and/or luteinizing hormone (LH) were tracked longitudinally. A subset of patients had free testosterone levels measured and a hypogonadal screening questionnaire administered. Patients receiving subsequent testosterone supplementation were assessed for symptomatic improvement. RESULTS: Mean total testosterone levels were -25% below the lower limit of normal (LLN) in 32 crizotinib-treated patients (27 of 32 patients below LLN, 84%) compared with +29% above LLN in 19 non-crizotinib-treated patients (6 of 19 below LLN, 32%), P = .0012. Levels of albumin and SHBG (which both bind testosterone) declined rapidly with crizotinib, but so did FSH, LH, and free testosterone, suggesting a centrally mediated, true hypogonadal effect. Mean free testosterone levels were -17% below LLN (19 of 25 patients below LLN, 76%). Eighty-four percent (16 of 19) with low free levels, and 79% (19/24) with low total levels had symptoms of androgen deficiency. Five of 9 patients (55%) with low testosterone given testosterone supplementation had improvement in symptoms, coincident with increases in testosterone above LLN. CONCLUSIONS: Symptoms of androgen deficiency and free or total/free testosterone levels should be tracked in male patients on crizotinib with consideration of testosterone replacement as appropriate.

New Human Leukocyte Antigen (HLA) Antibody Formation and Creatinine Elevation With Abaloparatide in Kidney Transplant Recipient.

A 39-year-old female with a history of kidney transplant presented to the endocrinology clinic for osteoporosis evaluation after sustaining an ankle fracture from a fall. Her kidney transplant regimen (mycophenolate mofetil 360 mg twice a day, tacrolimus 0.5 mg every morning and 0.5-1 mg every evening, prednisone 5 mg/day) and baseline creatinine (1.0-1.2 mg/dL) had been stable for several years. After an appropriate secondary workup, she was started on abaloparatide 80 µg subcutaneous daily injections for osteoporosis. She had a good initial biochemical response to therapy. However, 5 months after abaloparatide initiation she was found to have a new elevation in serum creatinine (1.17 to 1.69 mg/dL) despite stable serum tacrolimus trough levels, and two new human leukocyte antigen (HLA) antibodies (anti-HLA antibodies detected to Cw7 and DP28). Abaloparatide was stopped due to concern for immunogenicity. There was no evidence of rejection on kidney biopsy and she was restabilized on her transplant regimen with a new baseline creatinine of 1.3-1.6 mg/dL. The patient was subsequently started on teriparatide 20 µg daily subcutaneous injections for 2 years with good biochemical response, significant improvement in bone mineral density, and stable transplant regimen without additional signs of immunogenicity or rejection. This is the first case report to raise concern about immunogenicity with abaloparatide in solid organ transplant recipients. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Bad to the bones: prescribing of drugs for the prevention and treatment of osteoporosis in patients on chronic glucocorticoids.

Of patients prescribed systemic glucocorticoids, this study identifies the proportion prescribed osteoporosis pharmacologic treatment and associated characteristics. Overall, 13.2% of patients were prescribed osteoporosis pharmacologic treatment. Predictors included documented osteoporosis, past DXA or fracture, and provision of care within a department using embedded protocols, suggesting electronic medical record-based tools may be beneficial. PURPOSE: This study aimed to identify a cohort of patients at risk for glucocorticoid-induced osteoporosis based on their prescribed glucocorticoid regimens and to quantify the proportion who were also prescribed osteoporosis pharmacologic treatment. The secondary objective was to recognize patient characteristics associated with receiving such treatment. METHODS: A retrospective single-site cohort study used prescription order data to identify 7774 adults prescribed chronic glucocorticoids and measure the proportion also prescribed osteoporosis pharmacologic treatment. RESULTS: Of the total cohort, 1026/7774 (13.2%) had osteoporosis pharmacologic treatment prescribed. Of the subgroups prescribed a prednisone-equivalent of 5, 10, or 20 mg per day or more for at least 180 days, 584/4262 (13.7%), 153/1048 (14.6%), and 47/344 (13.7%) had treatment prescribed. Factors independently associated with osteoporosis pharmacologic treatment initiation included having osteoporosis or osteopenia on the problem list (OR = 4.45, 95% CI 3.70-5.34), history of dual-energy X-ray absorptiometry (DXA) screening (OR = 2.18, 95% CI 1.82-2.62), history of fracture (OR = 1.83, 95% CI 1.54-2.167), and longer duration of glucocorticoid use (OR = 1.33, 95% CI 1.10-1.59). The prescribing department was also a significant predictor of medication initiation, with cardiac transplant (OR = 6.04, 95% CI 3.97-9.17), oncology (OR = 4.11, OR 3.28-5.14), and lung transplant (OR = 1.51, 95% CI 1.08, 2.12) being positively correlated with this outcome, and nephrology (OR = 0.51, 95% CI 0.36-0.72) and kidney transplant (OR = 0.53, 95% CI 0.37, 0.75) being negatively correlated. CONCLUSION: Prescribing rate of osteoporosis pharmacologic treatment in patients using chronic glucocorticoids is low. Examining practices with higher prescribing rates may offer insight into improving protection against osteoporosis-induced fractures.

Gender-affirming hormone therapy, mental health, and surgical considerations for aging transgender and gender diverse adults.

As the transgender and gender diverse (TGD) population ages, more transfeminine and transmasculine individuals present to clinic to initiate or continue their gender-affirming care at older ages. Currently available guidelines on gender-affirming care are excellent resources for the provision of gender-affirming hormone therapy (GAHT), primary care, surgery, and mental health care but are limited in their scope as to whether recommendations require tailoring to older TGD adults. Data that inform guideline-recommended management considerations, while informative and increasingly evidence-based, mainly come from studies of younger TGD populations. Whether results from these studies, and therefore recommendations, can or should be extrapolated to aging TGD adults remains to be determined. In this perspective review, we acknowledge the lack of data in older TGD adults and discuss considerations for evaluating cardiovascular disease, hormone-sensitive cancers, bone health and cognitive health, gender-affirming surgery, and mental health in the older TGD population on GAHT.

Rapid-onset hypogonadism secondary to crizotinib use in men with metastatic nonsmall cell lung cancer.

BACKGROUND: The objective of this study was to document the differences in testosterone (T) levels between crizotinib-treated and noncrizotinib-treated patients with metastatic nonsmall cell lung cancer (NSCLC). METHODS: Testosterone levels were measured in 19 men with metastatic NSCLC who received crizotinib and in 19 men with metastatic NSCLC who did not receive crizotinib. Clinical characteristics of the patients were compared, and additional hormone assays were performed as appropriate. Two patients who began crizotinib and 4 patients who had dose interruptions or who stopped crizotinib therapy had serial hormone measurements, permitting the documentation of dynamic hormone changes on and off crizotinib treatment. RESULTS: Total T levels were low (<241 ng/dL) in 19 of 19 (100%) crizotinib-treated men and in 6 of 19 men (32%) with metastatic NSCLC who did not receive crizotinib (mean T levels, 131 ng/dL and 311 ng/dL, respectively; P = .0002). Only 1 in 5 patients who had anaplastic lymphoma kinase (ALK) gene rearrangements and had not yet received crizotinib had low T. The initiation of crizotinib in 2 patients who had previously normal T levels was associated with a rapid decreases in T and in luteinizing hormone and follicle stimulating hormone levels within 14 to 21 days. Discontinuation of crizotinib led to increases back to normal T levels. CONCLUSIONS: Crizotinib therapy caused rapid suppression of T levels in men. The current results indicated that the site of action must include a central (hypothalamic or pituitary) effect, but additional direct testicular effects could not be excluded. Further work is required to assess the correlation between low T levels and crizotinib side effects as well as the exact molecular mechanism and site of drug toxicity.

HIV infection and osteoporosis: pathophysiology, diagnosis, and treatment options.

As the population with HIV continues to age, specialists in HIV care are increasingly encountering chronic health conditions, which now include osteoporosis, osteopenia, and fragility fractures. The pathophysiology of the bone effects of HIV infection is complex and includes traditional risk factors for bone loss as well as specific effects due to the virus itself, chronic inflammation, and HAART. Examining risk factors for low bone density and screening of certain patients is suggested, and consideration should be given to treatment for those considered high risk for fracture.