Patients' Experiences With the Removal of a Ureteral Stent: Insights From In-depth Interviews With Participants in the USDRN STENTS Qualitative Cohort Study.

OBJECTIVE: To describe the experiences of patients undergoing stent removal in the USDRN Study to Enhance Understanding of Stent-Associated Symptoms (STENTS), a prospective, observational cohort study of patients with short-term ureteral stent placement post-ureteroscopy. METHODS: We conducted a qualitative descriptive study using in-depth interviews. Participants reflected on (1) painful or bothersome aspects of stent removal, (2) symptoms immediately after removal, and (3) symptoms in the days following removal. Interviews were audio-recorded, transcribed, and analyzed using applied thematic analysis. RESULTS: The 38 participants interviewed were aged 13-77 years, 55% female, and 95% White. Interviews were conducted 7-30 days after stent removal. Almost all participants (n = 31) described that they experienced either pain or discomfort during stent removal, but for most (n = 25) pain was of short duration. Many participants (n = 21) described anticipatory anxiety related to the procedure, and several (n = 11) discussed discomfort arising from lack of privacy or feeling exposed. Interactions with medical providers often helped put participants at ease, but also increased discomfort for some. Following stent removal, several participants described lingering pain and/or urinary symptoms, but these largely resolved within 24 hours. A few participants described symptoms persisting for more than a day post stent removal. CONCLUSION: These findings on patients' experiences during and shortly after ureteral stent removal, particularly the psychological distress they experienced, identify opportunities for improvement in patient care. Clear communication from providers about what to expect with the removal procedure, and the possibility of delayed pain, may help patients adapt to discomfort.

The Patient Voice: Stent Experiences After Ureteroscopy-Insights from In-Depth Interviews with Participants in the USDRN STENTS Nested Qualitative Cohort Study.

Purpose: Ureteral stents are commonly used after ureteroscopy and cause significant discomfort, yet qualitative perspectives on patients' stent experiences remain unknown. We describe psychological, functional, and interpersonal effects of post-ureteroscopy stents and whether additional patient-reported assessments may be needed. Materials and Methods: Using a qualitative descriptive study design, we conducted in-depth interviews with a nested cohort of participants in the STudy to Enhance uNderstanding of sTent-associated Symptoms (STENTS). Participants shared their symptoms with a post-ureteroscopy stent and described symptom bother and impact on daily activities. All interviews were audio-recorded, transcribed, and analyzed using applied thematic analysis. During analysis, participants' experiences with interference in daily activities were categorized into three groups based on their impact: minimal, moderate, and substantial. Results: All 39 participants experienced pain, although descriptions varied and differentiated between feelings of pain vs discomfort. Almost all experienced urinary symptoms. Only a few reported other physical symptoms, although several psychological aspects were identified. In the areas of sleep, mood, life enjoyment, work, exercise, activities of daily living, driving, childcare, and leisure/social activities, the stent had little impact on daily living among participants placed in the minimal group (n = 12) and far greater impact for participants in the substantial group (n = 8). For patients in the moderate group (n = 19), some daily activities were moderately or substantially affected, whereas other activities were minimally affected. Conclusions: Counseling to better prepare patients for the impact of stent-associated symptoms may help mitigate symptom burden. While existing instruments adequately cover most symptoms, additional assessments for other domains, particularly psychological factors, may be needed.

Risk Factors for Increased Stent-associated Symptoms Following Ureteroscopy for Urinary Stones: Results From STENTS.

PURPOSE: The STudy to Enhance uNderstanding of sTent-associated Symptoms sought to identify risk factors for pain and urinary symptoms, as well as how these symptoms interfere with daily activities after ureteroscopy for stone treatment. MATERIALS AND METHODS: This prospective observational cohort study enrolled patients aged ≥12 years undergoing ureteroscopy with ureteral stent for stone treatment at 4 clinical centers. Participants reported symptoms at baseline; on postoperative days 1, 3, 5; at stent removal; and day 30 post-stent removal. Outcomes of pain intensity, pain interference, urinary symptoms, and bother were captured with multiple instruments. Multivariable analyses using mixed-effects linear regression models were identified characteristics associated with increased stent-associated symptoms. RESULTS: A total of 424 participants were enrolled. Mean age was 49 years (SD 17); 47% were female. Participants experienced a marked increase in stent-associated symptoms on postoperative day 1. While pain intensity decreased ∼50% from postoperative day 1 to postoperative day 5, interference due to pain remained persistently elevated. In multivariable analysis, older age was associated with lower pain intensity (P = .004). Having chronic pain conditions (P < .001), prior severe stent pain (P = .021), and depressive symptoms at baseline (P < .001) were each associated with higher pain intensity. Neither sex, stone location, ureteral access sheath use, nor stent characteristics were drivers of stent-associated symptoms. CONCLUSIONS: In this multicenter cohort, interference persisted even as pain intensity decreased. Patient factors (eg, age, depression) rather than surgical factors were associated with symptom intensity. These findings provide a foundation for patient-centered care and highlight potential targets for efforts to mitigate the burden of stent-associated symptoms.

Bone health outcomes in post-lung transplant patients with cystic fibrosis.

BACKGROUND: Osteoporosis is a common comorbidity in patients with cystic fibrosis (CF). Although lung transplantation (LTx) improves quality of life of CF patients, there is little research examining long-term bone health outcomes following LTx in these patients. METHODS: Data were collected on 59 patients who underwent LTx between 2006 and 2019, including 30 with CF and 29 without CF. We compared baseline characteristics, long-term bone mineral density (BMD) trends, and fracture incidence between the two patient populations, and examined factors associated with post-LTx fractures in CF patients. RESULTS: Compared with non-CF patients, patients with CF were younger, had lower body mass index, and lower baseline BMD Z-scores at the lumbar spine, femoral neck, and total hip (all p<0.001). BMD at all sites declined in both groups in the first year post-LTx. In subsequent years, CF patients exhibited better BMD recovery relative to pre-transplantation, but continued to have lower BMD post-LTx. Post-transplant fractures occurred in 30% and 34% of CF and non-CF patients, respectively. CF patients who developed fractures after LTx had significantly lower BMD and lower pre-transplantation percent predicted forced expiratory volume in one second (FEV1%). CONCLUSIONS: Although CF patients exhibit better BMD recovery following LTx compared to their non-CF counterparts, CF patients start with significantly lower pre-LTx BMD and experience a similarly high rate of post-LTx fractures. These findings highlight the unique contribution of the CF disease process to bone health, as well as a clear need for better prevention and treatment of osteoporosis in CF patients before and after LTx.

Evaluation of an association between RANKL and OPG with bone disease in people with cystic fibrosis.

BACKGROUND: As people with Cystic Fibrosis (CF) live longer, extra-pulmonary complications such as CF-related bone disease (CFBD) are becoming increasingly important. The etiology of CFBD is poorly understood but is likely multifactorial. Bones undergo continuous remodeling via pathways including RANK (receptor activator of NF-κB)/sRANKL (soluble ligand)/OPG (osteoprotegerin). We sought to examine the association between sRANKL (stimulant of osteoclastogenesis) and OPG levels (inhibitor of osteoclast formation) and CFBD to investigate their potential utility as biomarkers of bone turnover in people with CF. METHODS: We evaluated sRANKL and OPG in plasma from people with CF and healthy controls (HC) and compared levels in those with CF to bone mineral density results. We used univariable and multivariable analysis to account for factors that may impact sRANKL and OPG. RESULTS: We found a higher median [IQR] sRANKL 10,896pg/mL [5,781-24,243] CF; 2,406pg.mL [659.50-5,042] HC; p= 0.0009), lower OPG 56.68pg/mL [36.28-124.70] CF; 583.20pg/mL [421.30-675.10] HC; p < 0.0001), and higher RANKL/OPG in people with CF no BD than in HC (p < 0.0001). Furthermore, we found a higher RANKL/OPG ratio 407.50pg/mL [214.40-602.60] CFBD; 177.70pg/mL [131.50-239.70] CF no BD; p = 0.007) in people with CFBD versus CF without bone disease. This difference persisted after adjusting for variables thought to impact bone health. CONCLUSIONS: The current screening recommendations of imaging for CFBD may miss important markers of bone turnover such as the RANKL/OPG ratio. These findings support the investigation of therapies that modulate the RANK/RANKL/OPG pathway as potential therapeutic targets for bone disease in CF.

Romosozumab-aqqg in the Treatment of Osteoporosis in a Patient With Hypophosphatasia.

Hypophosphatasia is a rare, inherited condition that causes osteomalacia and recurrent fractures. Therapeutic options for osteoporosis in patients with hypophosphatasia are limited because of concerns for a greater likelihood of atypical femoral fractures with antiresorptive agents. We report here the case of a patient with hypophosphatasia and osteoporosis who was treated with romosozumab-aqqg (Romo). An 81-year-old woman presented for management of osteoporosis with multiple fractures. She experienced a decline in bone mineral density over 20 years despite sequential osteoporosis treatment with oral bisphosphonates, hormone replacement therapy, teriparatide, and denosumab. Hypophosphatasia was suspected because of low serum alkaline phosphatase levels and was confirmed by genetic testing. After diagnosing hypophosphatasia, bone mineral density continued to decline and a trial of Romo was begun. After 1 year of Romo therapy, bone mineral density improved by 21%, and 10% at the lumbar spine and total hip, respectively. These changes were substantially greater than what she had experienced with prior teriparatide therapy. Blood alkaline phosphatase remained low on Romo. To our knowledge, this is the first report of a patient with hypophosphatasia and osteoporosis treated with Romo. In our patient, Romo did not significantly impact serum alkaline phosphatase, but improved bone mineral density significantly. In conclusion, Romo is a potential treatment option for osteoporosis in patients with hypophosphatasia for whom limited alternatives exist.

Quality of life impact and recovery after ureteroscopy and stent insertion: insights from daily surveys in STENTS.

BACKGROUND: Our objective was to describe day-to-day evolution and variations in patient-reported stent-associated symptoms (SAS) in the STudy to Enhance uNderstanding of sTent-associated Symptoms (STENTS), a prospective multicenter observational cohort study, using multiple instruments with conceptual overlap in various domains. METHODS: In a nested cohort of the STENTS study, the initial 40 participants having unilateral ureteroscopy (URS) and stent placement underwent daily assessment of self-reported measures using the Brief Pain Inventory short form, Patient-Reported Outcome Measurement Information System measures for pain severity and pain interference, the Urinary Score of the Ureteral Stent Symptom Questionnaire, and Symptoms of Lower Urinary Tract Dysfunction Research Network Symptom Index. Pain intensity, pain interference, urinary symptoms, and bother were obtained preoperatively, daily until stent removal, and at postoperative day (POD) 30. RESULTS: The median age was 44 years (IQR 29,58), and 53% were female. The size of the dominant stone was 7.5 mm (IQR 5,11), and 50% were located in the kidney. There was consistency among instruments assessing similar concepts. Pain intensity and urinary symptoms increased from baseline to POD 1 with apparent peaks in the first 2 days, remained elevated with stent in situ, and varied widely among individuals. Interference due to pain, and bother due to urinary symptoms, likewise demonstrated high individual variability. CONCLUSIONS: This first study investigating daily SAS allows for a more in-depth look at the lived experience after URS and the impact on quality of life. Different instruments measuring pain intensity, pain interference, and urinary symptoms produced consistent assessments of patients' experiences. The overall daily stability of pain and urinary symptoms after URS was also marked by high patient-level variation, suggesting an opportunity to identify characteristics associated with severe SAS after URS.

Androgen Deprivation Therapy Differentially Impacts Bone and Muscle in the Short Term in Physically Active Men With Prostate Cancer.

Androgen deprivation therapy (ADT) is a cornerstone of advanced prostate cancer (PCa) therapy. Its use is associated with a loss of bone mineral density (BMD) and a greater risk of falls and osteoporotic fractures. In this prospective cohort study, we examined the impact of ADT on muscle and bone strength in men initiating ADT for PCa. Participants were evaluated at three time points: immediately before (week 0), and 6 and 24 weeks after ADT initiation. Study measures included fasting blood levels (for markers of muscle and bone metabolic activity), MRI and QCT imaging (for muscle fat content, and bone density and architecture), and validated clinical tests of muscle strength and gait. Sixteen men completed all study visits. At baseline and throughout the study, participants exercised a median of four times/week, but still experienced weight gain (+2.0 kg at week 24 versus week 0, p = 0.004). Biochemically, all men sustained dramatic early and persistent reductions in sex hormones post-ADT, along with a progressive and significant increase in serum C-telopeptide of type I collagen (CTX, +84% at week 24 versus week 0). There was a trend for rise in serum sclerostin (p = 0.09) and interleukin 6 (IL-6) (p = 0.08), but no significant change in serum myostatin (p = 0.99). Volumetric BMD by QCT declined significantly at the femoral neck (-3.7% at week 24 versus week 0), particularly at the trabecular compartment. On MRI, there were no significant changes in thigh muscle fat fraction. On physical testing, men developed weaker grip strength, but experienced no worsening in lower extremity and lumbar spine muscle strength, or on functional tests of gait. In conclusion, in physically active men, ADT for 24 weeks results in a significant increase in bone resorption and reduction in BMD, but nonsignificant changes in thigh muscle quality (on imaging) or strength and gait (on functional testing). © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Impact of age and renal function on urine chemistry in patients with calcium oxalate kidney stones.

Nephrolithiasis is associated with an increased risk of chronic kidney disease, and its incidence varies with age. However, little is known on the combined impact of aging and declining renal function on urinary risk factors for calcium oxalate stone formation. A retrospective analysis was performed on 24-h urine collections from 993 calcium oxalate stone-forming patients. We first tested for interactions between age and creatinine clearance on various urinary determinants of calcium oxalate nephrolithiasis, and then examined their separate and combined effects in univariable and multivariable analyses adjusting for demographic and biochemical covariates. We identified significant interactions between age and creatinine clearance in predicting 24-h urine pH, calcium, and citrate. In view of the small number of stone formers with low creatinine clearance, we limited further regression analyses to patients with creatinine clearance ≥ 60 mL/min. In multivariable analyses, urine citrate, oxalate, and total volume were positively correlated with age, whereas urine pH, citrate, calcium, oxalate, total volume, and RSR of calcium oxalate all significantly decreased with lower creatinine clearance. A decrease in creatinine clearance from 120 to 60 mL/min was associated with clinically significant decreases in the daily excretion rate of citrate (by 188 mg/day), calcium (by 33 mg/day), and oxalate (by 4 mg/day), and in RSR calcium oxalate (by 1.84). Age and creatinine clearance are significant and independent predictors of several urinary determinants of calcium oxalate nephrolithiasis. The impacts of aging and declining renal function should be considered during the management of calcium oxalate stone-forming patients.

Study to Enhance Understanding of Stent-Associated Symptoms: Rationale and Study Design.

Background: Ureteral stents are commonly employed after ureteroscopy to treat urinary stone disease, but the devices impose a substantial burden of stent-associated symptoms (SAS), including pain and urinary side effects. The NIDDK (National Institute of Diabetes and Digestive and Kidney Diseases) Urinary Stone Disease Research Network sought to develop greater understanding of SAS causes and severity among individuals treated ureteroscopically for ureteral or renal stones. Materials and Methods: We designed a prospective, observational cohort study comprising adolescents and adults undergoing ureteroscopic intervention for ureteral or renal stones. Participants will undergo detailed symptom assessment using validated questionnaires, a psychosocial assessment, and detailed collection of clinical and operative data. Quantitative sensory testing will be utilized to assess pain sensitization. In addition, a small cohort (∼40 individuals) will participate in semi-structured interviews to develop more granular information regarding their stent symptoms and experience. Biospecimens (blood and urine) will be collected for future research. Results: The Study to Enhance Understanding of sTent-associated Symptoms (STENTS) enrolled its first participant in March 2019 and completed nested qualitative cohort follow-up in August 2019. After a planned pause, enrollment for the main study cohort resumed in September 2019 and is expected to be completed in 2021. Conclusion: STENTS is expected to provide important insights into the mechanisms and risk factors for severe ureteral SAS after ureteroscopy. These insights will generate future investigations to mitigate the burden of SAS among individuals with urinary stone disease.

Association Between Bone Mineral Density and Depressive Symptoms in a Population-Based Sample.

OBJECTIVE: This analysis was conducted to determine the relationship between bone mineral density (BMD) and depressive symptoms in a population-based cohort. METHODS: Data were extracted from the second phase of the Dallas Heart Study (DHS-2), a large, multiethnic population sample in Dallas County, Texas, from September 1, 2007, to December 31, 2009. Depressive symptom severity was measured with the 16-item Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR16), which is derived from DSM-IV major depressive disorder criteria. BMD was measured using dual-energy x-ray absorptiometry. Multiple linear regressions examined the relationship between QIDS-SR16 score and BMD controlling for age, body mass index, sex, ethnicity, smoking status, alcohol use status, serum 25-hydroxyvitamin D concentration, antidepressant use, and physical activity as measured by total vigorous and moderate metabolic equivalents. Subgroup analyses explored differences related to age. RESULTS: QIDS-SR16 score was not a significant predictor of either lumbar spine or total hip T-score (ß = -0.01, P = .61 and ß = -0.02, P = .39) in the overall population (n = 2,285). There was a significant negative interaction term between age and QIDS-SR16 group (ß = -0.01, P = .01). In participants aged 60 years or older (n = 465), QIDS-SR16 score was a significant predictor of BMD at the lumbar spine and total hip (ß = -0.14, P = .003 and ß = -0.12, P = .006, respectively). CONCLUSIONS: QIDS-SR16 score did not significantly predict BMD in the overall DHS-2 sample. There was, however, a significant association observed in participants aged ≥ 60 years. Results suggest that diagnosis and treatment of depressive symptoms may be of clinical importance in older individuals, a subgroup at high risk for osteoporosis and fractures.

The Differential Effects of Human Immunodeficiency Virus and Hepatitis C Virus on Bone Microarchitecture and Fracture Risk.

Background: Human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected individuals have a significantly greater osteoporotic fracture risk than HIV-monoinfected persons, despite the fact that HIV/HCV coinfection has not been associated with lower bone mineral density (BMD) than HIV or HCV alone. To evaluate if changes in bone microarchitecture, measured by trabecular bone score (TBS), could explain these differences, we performed a prospective, cross-sectional cohort study of virologically suppressed HIV-infected subjects, untreated HCV-infected subjects, HIV/HCV-coinfected subjects, and uninfected controls. Methods: We enrolled 532 male subjects: 57 HIV/HCV coinfected, 174 HIV infected, 123 HCV infected, and 178 controls. We conducted analysis of covariance comparing BMD and TBS between groups, controlling for age, race, body mass index, and smoking. We used linear regression to evaluate predictors of BMD and TBS and evaluated the effects of severity of HCV infection and tenofovir disoproxil fumarate use. Results: Despite both infections being associated with decreased BMD, only HCV, but not HIV, was associated with lower TBS score. Also, HIV/HCV-coinfected subjects had lower TBS scores than HIV-monoinfected, HCV-monoinfected, and uninfected subjects. Neither the use of TDF or HCV viremia nor the severity of HCV liver disease was associated with lower TBS. Conclusions: HCV infection is associated with microarchitectural changes at the lumbar spine as assessed by the low TBS score, suggesting that microstructural abnormalities underlie some of the higher fracture risk in HCV infection. TBS might improve fracture risk prediction in HCV infection.

Longitudinal changes in serum 25-hydroxyvitamin D in the Dallas Heart Study.

CONTEXT: While the prevalence of vitamin D deficiency is well described in various populations, limited data are available regarding longitudinal variation in serum 25-hydroxyvitamin D concentrations. OBJECTIVES: To evaluate the temporal trends in serum 25(OH)D, prevalence of vitamin D deficiency and factors influencing these trends. PARTICIPANTS, DESIGN AND SETTING: Adults enrolled in the Dallas Heart Study, a longitudinal, probability-based, multiethnic, population study in Dallas, Texas, USA. MAIN OUTCOME MEASURES: Prevalence of vitamin D deficiency and predictors of change in serum 25(OH)D. RESULTS: A total of 2045 participants had serum 25(OH)D measured on two occasions (2000-2002 and 2007-2009) at a median interval of 7 years. Serum 25(OH)D decreased (42.7-39.4 nmol/L, P<.001) and the prevalence of vitamin D deficiency [25(OH)D <50 nmol/L] increased significantly (60.6%-66.4%, P<.0001) despite vitamin D supplementation increasing over the interval (7.2%-23.0%; P<.0001). In a multivariable model adjusting for sex, race, BMI, age, season of blood draw, smoking and exercise, a greater decline in serum 25(OH)D was noted in men compared with women (-8.0 vs -3.5 nmol/L, P<.0001), in participants of Hispanic ethnicity vs White and Black ethnicity (P<.0001), in nonobese vs obese participants (-7.2 vs -4.0 nmol/L, P=.005) and in nonusers vs users of vitamin D supplements (-5.7 vs -1.7 nmol/L, P=.032). CONCLUSIONS: Despite increased vitamin D supplementation, serum 25(OH)D decreased in an ethnically diverse cohort of Dallas County residents between 2000-2002 and 2007-2009. Features most predictive of a decline in serum 25(OH)D include male sex, Hispanic ethnicity and weight gain.

Vitamin-D status and mineral metabolism in two ethnic populations with sarcoidosis.

Vitamin-D insufficiency and sarcoidosis are more common and severe in African Americans (AA) than Caucasians. In sarcoidosis, substrate-dependent extrarenal 1,25-dihydroxyvitamin-D (1,25-(OH)2D) production is thought to contribute to hypercalciuria and hypercalcemia, and vitamin-D repletion is often avoided. However, the anti-inflammatory properties of vitamin-D may also be beneficial. We prospectively examined serum vitamin-D levels, calcium balance, and the effects of vitamin-D repletion in 86 AA and Caucasian patients with biopsy-proven active sarcoidosis from the USA (US) and Italy (IT) in university-affiliated outpatient clinics. Clinical features, pulmonary function, and calciotropic hormones were measured. 16 patients with vitamin-D deficiency and normal serum ionized calcium (Ca(2+)) were treated with oral ergocalciferol (50,000 IU/week) for 12 weeks. Baseline mineral parameters were similar in US (93% AA) and IT (95% Caucasian) patients irrespective of glucocorticoid treatment. Pulmonary dysfunction was less pronounced in IT patients. Nephrolithiasis (in 11% US, 17% IT patients) was associated with higher urinary calcium excretion. Vitamin-D deficiency was not more prevalent in patients compared to the respective general populations. As serum 25-hydroxyvitamin-D (25-OHD) rose postrepletion, serum 1,25-(OH)2D, γ-globulins, and the previously elevated angiotensin converting enzyme (ACE) levels declined. Asymptomatic reversible increases in Ca(2+) or urinary calcium/creatinine (Ca/Cr) developed in three patients during repletion. In conclusion, Caucasian and AA patients show similar calcium and vitamin D profiles. The higher prevalence of hypercalciuria and nephrolithiasis in sarcoidosis is unrelated to endogenous vitamin-D levels. Vitamin-D repletion in sarcoidosis is generally safe, although calcium balance should be monitored. A hypothesis that 25-OHD repletion suppresses granulomatous immune activity is provided.

Mechanisms of bone disease in HIV and hepatitis C virus: impact of bone turnover, tenofovir exposure, sex steroids and severity of liver disease.

OBJECTIVE: Both HIV and hepatitis C virus (HCV) infections are associated with higher osteoporotic fracture risk. Increased bone turnover, liver fibrosis, tenofovir (TDF) use or hormonal imbalances are possible underlying mechanisms. DESIGN: This prospective, cross-sectional study assessed 298 male volunteers with either virologically suppressed HIV or untreated HCV mono-infections, HIV/HCV co-infection and noninfected controls. METHODOLOGY: Study participants underwent bone mineral density (BMD) by dual-energy x-ray absorptiometry and measurement of bone turnover markers [BTM: C-telopeptide (CTX) and osteocalcin (OC)], insulin-like growth factor-1 (IGF-1), the sex steroids testosterone (T) and estradiol (E2), and the aspartate aminotransferase-to-platelet ratio index (APRI). Impact of HIV and HCV status on BMD was evaluated in multivariate models adjusting for APRI score, BTM, TDF exposure, IGF-1, and sex steroids. RESULTS: HIV and HCV status independently predicted lower BMD, controlling for age, race, BMI, and smoking (P = 0.017 and P = 0.010, respectively), whereas APRI did not (P = 0.84). HIV was associated with increased bone resorption (CTX: P < 0.001) and formation (OC: P = 0.014), whereas HCV infection was not associated with CTX (P = 0.30) or OC (P = 0.36). TDF exposure was associated with lower BMD (P < 0.01). IGF-1 was significantly decreased in HCV and increased in HIV. Tumor necrosis factor-α (P = 0.98), IGF-1 (P = 0.80), bioavailable T (P = 0.45) and E2 (P = 0.27) were not associated with BMD and did not attenuate the impact of HIV or HCV on BMD. CONCLUSION: HIV and TDF exposure decrease BMD through increased bone turnover, although the lower BMD in HCV is not explained by a high turnover state. Neither virus' effect on BMD is likely mediated through increased inflammation, liver fibrosis, IGF-1, or sex steroids.

Relationship between serum uric Acid and bone mineral density in the general population and in rats with experimental hyperuricemia.

UNLABELLED: Higher serum uric acid concentrations have been associated with higher bone mineral density (BMD) in observational studies of older men and perimenopausal or postmenopausal women, prompting speculation of a potential protective effect of uric acid on bone. Whether this relationship is present in the general population has not been examined and there is no data to support causality. We conducted a cross-sectional analysis of a probability sample of the U.S. POPULATION: Demographic data, dietary intake, lifestyle risk factors and physical activity assessment data, serum biochemistry including serum uric acid, and BMD were obtained from 6759 National Health and Nutrition Examination Survey (NHANES; 2005-2010) participants over 30 years of age. In unadjusted analyses, higher serum uric acid levels were associated with higher BMD at the femoral neck, total hip, and lumbar spine in men, premenopausal women, and postmenopausal women not treated with estrogen. However, these associations were no longer statistically significant after adjustment for potential confounders, including age, body mass index (BMI), black race, alcohol consumption, estimated glomerular filtration rate (eGFR), serum alkaline phosphatase, and C-reactive protein (CRP). This is in contradistinction to some prevailing conclusions in the literature. To further examine the causal effect of higher serum uric acid on skeletal health, including biomechanical properties that are not measurable in humans, we used an established rat model of inducible mild hyperuricemia. There were no differences in BMD, bone volume density, and bone biomechanical properties between hyperuricemic rats and normouricemic control animals. Taken together, our data do not support the hypothesis that higher serum uric acid has protective effects on bone health.

Effects of sex and postmenopausal estrogen use on serum phosphorus levels: a cross-sectional study of the National Health and Nutrition Examination Survey (NHANES) 2003-2006.

BACKGROUND: Elevation of serum phosphorus concentrations has been associated with cardiovascular events in older women and men. Whether age, sex, or estrogen therapy is associated with different phosphorus levels is unknown. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 7,005 participants in the National Health and Nutrition Examination Survey (NHANES) 2003-2006. PREDICTORS: Demographic data; body measurement indexes; dietary intake by 24-hour dietary recall and food-frequency questionnaire; data for reproductive health, prescription medication, cardiovascular disease, osteoporosis, and diabetes mellitus obtained by questionnaire; and blood chemistry indexes. OUTCOMES & MEASUREMENTS: Serum phosphorus concentrations. RESULTS: In both males and premenopausal females, serum phosphorus levels decline progressively with age. In males, the decline continues over the entire age range of 21-85 years. In contrast, in females, serum phosphorus levels increase between ages 46-60 years (sex×age interaction; P<0.001). The increase in serum phosphorus levels in older women is independent of changes in serum parathyroid hormone levels, daily dietary phosphorus intake, and estimated glomerular filtration rate. In analysis of covariance, we show that postmenopausal women receiving estrogen therapy have significantly lower serum phosphorus levels than non-estrogen users after adjusting for age, race, body mass index, daily dietary phosphorus intake, and serum albumin, serum parathyroid hormone, and 25-hydroxyvitamin D levels (3.83 vs 3.98mg/dL; P<0.001). LIMITATIONS: The study was cross-sectional in design and estrogen therapy was not randomly assigned or concealed. Important phosphorus regulatory factors such as serum fibroblast growth factor 23 and klotho were not available in the study. CONCLUSIONS: Estrogen status may account for the difference in serum phosphorus levels in postmenopausal women.

Normocalcemic hyperparathyroidism and hypoparathyroidism in two community-based nonreferral populations.

CONTEXT: Normocalcemic primary hyperparathyroidism is typically identified after referral to a specialty clinic. At diagnosis, patients demonstrate features seen in hypercalcemic primary hyperparathyroidism. Normocalcemic hypoparathyroidism has been discovered after hypocalcemia unmasked after bisphosphonate administration. OBJECTIVE: We hypothesized that screening unselected, nonreferral populations, such as The Osteoporotic Fractures in Men (MrOS) study and Dallas Heart Study (DHS), would identify asymptomatic subjects with normocalcemic hyperparathyroidism and hypoparathyroidism. METHODS: Normocalcemic hyperparathyroidism was defined as serum PTH greater than the upper reference range with normal albumin-adjusted serum calcium, excluding common secondary causes (renal failure [estimated glomerular filtration rate <60 mL/min], 25-hydroxyvitamin D <20 ng/mL, and thiazide use), and normocalcemic hypoparathyroidism as PTH below the reference range with normocalcemia. Cross-sectional data were obtained from MrOS, and longitudinal data (baseline and 8 years) from DHS. RESULTS: In 2364 men from MrOS, we identified 9 with normocalcemic hyperparathyroidism (prevalence 0.4%) and 26 with normocalcemic hypoparathyroidism (1.1%). In 3450 men and women from DHS, we identified 108 with normocalcemic hyperparathyroidism (3.1%) and 68 with normocalcemic hypoparathyroidism (1.9%). Of the 108 normocalcemic hyperparathyroid subjects, 64 had follow-up data. Hypercalcemic primary hyperparathyroidism developed in 1 subject whereas 13 (0.6% of the follow-up cohort) showed persistently elevated PTH levels with normocalcemia. Of the 26 normocalcemic hypoparathyroid subjects with follow-up data, none developed overt hypoparathyroidism and 2 (0.09%) had persistent evidence of normocalcemic hypoparathyroidism. CONCLUSIONS: This study documents normocalcemic primary hyperparathyroidism and hypoparathyroidism identified among community-dwelling individuals. Larger studies are needed to determine the true prevalence and natural history of these parathyroid disorders.

Hepatitis C co-infection and severity of liver disease as risk factors for osteoporotic fractures among HIV-infected patients.

Osteoporosis is increasingly reported in the aging HIV-positive population, and co-infection with hepatitis C virus (HCV) may further increase the risk of osteoporosis. However, it remains unclear whether HCV-related increased fracture risk is a function of the severity of liver disease. We calculated the time-updated alanine aminotransferase to platelet ratio index (APRI) score (an indirect marker of hepatic fibrosis) in all HIV-infected patients enrolled in the Veterans Affairs' Clinical Case Registry between 1984 and 2009. The association between HCV co-infection and incident osteoporotic fracture (defined as closed wrist, vertebral, or hip fracture) was assessed in univariate and multivariate Cox survival models adjusting for traditional risk factors for osteoporosis and APRI score or the presence of cirrhosis. A total of 772 osteoporotic fractures were identified among 56,660 HIV-infected patients (98.1% male; 31.3% HCV co-infected; median age 44.0 years) contributing 305,237 patient-years of follow-up. Fracture rates were significantly higher among HIV/HCV patients than HIV-only patients (2.57 versus 2.07/1000 patient-years, relative risk = 1.24, p < 0.0001). In a Cox multivariable model including age, race, smoking, drug use, body mass index, and antiretroviral therapy, HCV co-infection remained an independent predictor of osteoporotic fractures after controlling for presence of cirrhosis (hazard ratio [HR] = 1.32; p <0.001) or APRI score (HR = 1.30; p = 0.003). Among HIV/HCV co-infected patients, cirrhosis strongly predicted osteoporotic fractures (HR = 1.65; 95% confidence interval [CI] 1.11-2.44; p = 0.012), but APRI score was a weaker predictor (HR = 1.008; 95% CI 1.002-1.014; p = 0.015). In conclusion, among HIV-infected patients, severity of liver disease partly explains the HCV-associated increased risk of osteoporotic fractures. Other determinants of this increased risk remain to be defined.