Degree of Albuminuria is Associated With Increased Risk of Fragility Fractures Independent of Estimated GFR.

Introduction: Fragility fractures are common in persons with chronic kidney disease (CKD); however, the association between fragility fractures and albuminuria is not well-studied. The primary objective of this study is to determine the association of albuminuria with incident risk of fragility fractures. The secondary objective is to examine the risk of fragility fracture by estimated glomerular filtration rate (eGFR) and Kidney Disease Improving Global Outcomes (KDIGO) risk categories. Methods: Community dwelling adults residing in Alberta, Canada who had at least 1 creatinine and albuminuria measurement between April 1, 2008 and March 31, 2019 participated in the study (N = 2.72 million). Incident fragility fractures were identified using Canadian Chronic Disease Surveillance Systems Osteoporosis Working Group algorithms. Albuminuria was categorized as none/mild (albumin-to-creatinine ratio [ACR] <30 mg/g, protein-to-creatinine ratio [PCR] <150 mg/g, trace/negative dipstick); moderate (ACR 30-300 mg/g, PCR 150-500 mg/g, 1+ dipstick) or severe (ACR >300 mg/g, PCR >500 mg/g, ≥2+ dipstick). Multivariable analysis controlled for 42 variables. Results: Patients with severe albuminuria had an increased risk of hip fracture (odds ratio [OR] = 1.37; 95% confidence interval [CI] 1.28, 1.47]), vertebral fracture (OR = 1.31; 95% CI 1.21, 1.41) and any-type fracture (OR = 1.22; 95% CI 1.17, 1.28) compared with patients with none/mild albuminuria. Patients in the most severe KDIGO risk category had an increased risk of hip fracture (OR = 1.22; 95% CI 1.16, 1.29), vertebral fracture (OR = 1.18; 95% CI 1.09, 1.26) and any type of fracture (OR = 1.25; 95% CI 1.21, 1.30). Conclusion: This study demonstrates the important role of albuminuria as a risk factor for fragility fractures in CKD and may help inform risk stratification and prevention strategies in this high-risk population category.

Factors affecting thyroid nodule fine needle aspiration non-diagnostic rates: a retrospective association study of 1975 thyroid biopsies.

BACKGROUND: Thyroid nodules are common in clinical practice, and it is important to distinguish benign nodules, the vast majority, from malignant ones. Non-diagnostic (ND) samples have the potential to delay or mis-diagnose or lead to unnecessary surgeries, and it is important to examine what factors influence the ND rate. Prior literature has suggested that the impact of bedside cytology on ND rate is dependent on the initial adequacy rate, whereby higher ND rates benefit most from bedside cytology. We aim to compare the impact of bedside adequacy review between specialist groups who perform high volume thyroid biopsies with low initial ND rates. METHODS: We reviewed the cytopathology results of 1975 thyroid nodule FNAs performed between January 1, 2017 to December 31, 2017 in a multi-centre Canadian city, and the corresponding histopathology reports of 340 resected nodules. Descriptive variables were used to describe the data along with chi-squared testing and univariate logistic regression. RESULTS: The FNA biopsies were performed by three different speciality groups, which differed by procedural volume: radiology performed the most at 1171, pathology performed 655 and surgery performed 103. We could not define the operator for 45 of the nodules. The ND rate was lowest in the speciality groups with highest procedural volume, 3.4 % in pathology and 8.3 % in radiology, compared to 37.9 % in surgery (p < 0.001). Completion of bedside cytology rapid onsite evaluation (ROSE) significantly reduced the ND rate from 16.7 to 4.2 % for all samples (p < 0.001). When ROSE was compared with non-ROSE within a high procedural group (radiology), it further reduced the ND rate from 12.5 to 5.1 % (p < 0.001). Of the 340 resected nodules, 10.7 % (18) were in the ND category, of which 28 % (5/18) of these were found to be malignant (4 papillary carcinoma and 1 lymphoma). CONCLUSIONS: The results from this study demonstrate that thyroid FNAs performed with bedside ROSE can significantly reduce the ND rate compared with non-ROSE, even in experienced groups with low initial ND rates. It is therefore imperative that care providers managing patients with thyroid nodules ensure that thyroid FNAs are referred to specialized individuals/groups who do high volume, and ideally with the use of bedside ROSE, whether provided by a cytotechnologist or a pathologist.

Parity and lactation are not associated with incident fragility fractures or radiographic vertebral fractures over 16 years of follow-up: Canadian Multicentre Osteoporosis Study (CaMos).

Parity and lactation showed no associations with incident clinical fragility fractures or radiographic vertebral compression fractures in the 16-year CaMos prospective study. Parity was associated with slightly greater decline in femoral neck but not hip or spine areal bone mineral density (aBMD), while lactation showed no associations with aBMD change. PURPOSE: Pregnancy and especially lactation cause loss of bone mass and microarchitectural changes, which temporarily increase fracture risk. After weaning, aBMD increases but skeletal microarchitecture may be incompletely restored. Most retrospective clinical studies found neutral or even protective associations of parity and lactation with fragility fractures, but prospective data are sparse. CaMos is a randomly selected observational cohort that includes ~ 6500 women followed prospectively for over 16 years. METHODS: We determined whether parity or lactation were related to incident clinical fragility fractures over 16 years, radiographic (morphometric and morphologic) vertebral fractures over 10 years, and aBMD change (spine, total hip, and femoral neck) over 10 years. Parity and lactation duration were analyzed as continuous variables in predicting these outcomes using univariate and multivariate regression analyses. RESULTS: Three thousand four hundred thirty-seven women completed 16 years of follow-up for incident clinical fractures, 3839 completed 10 years of morphometric vertebral fracture assessment, 3788 completed 10 years of morphologic vertebral fracture assessment, and 4464 completed 10 years of follow-up for change in aBMD. In the multivariate analyses, parity and lactation duration showed no associations with clinical fragility fractures, radiographic vertebral fractures, or change in aBMD, except that parity associated with a probable chance finding of a slightly greater decline in femoral neck aBMD. CONCLUSIONS: Parity and lactation have no adverse associations with clinical fragility or radiographic vertebral fractures, or the rate of BMD decline over 10 years, in this prospective, multicenter study of a randomly selected, population-based cohort of women.

Spine bone mineral density increases after 6 months of exclusive lactation, even in women who keep breastfeeding.

This pilot study enrolled 31 women who had breastfed exclusively for 6 months. Lumbar and thoracic BMD increased 4 and 5%, respectively. Femoral neck and total body BMD did not change. Return of menses and progestin-only pill use were two potential signals that predicted a greater increase in BMD. PURPOSE/INTRODUCTION: The skeleton is resorbed during lactation to provide much of the calcium content of milk. After lactation ceases, these deficits in skeletal mineral content are largely restored, such that lactation has a neutral or protective effect against the long-term risk of low bone mineral density (BMD), osteoporosis, and fragility fractures. We hypothesized that a large observational study may identify the factors that predict a greater increase in BMD after lactation ceases. A pilot study was first needed to test feasibility and the magnitude of expected BMD change. METHODS: We undertook Factors Affecting Bone formation after Breastfeeding Pilot (FABB Pilot), which enrolled women who had breastfed exclusively for 6 months and planned to wean soon. The main outcome was change in BMD between enrolment and 6 months later. RESULTS: Thirty-one women were recruited and completed both time points. Lumbar and thoracic spine BMD increased 4 and 5%, respectively; there was no significant change in femoral neck and total body BMD. Most women did not wean their babies as planned but continued to breastfeed multiple times per day. Despite this, a significant increase in BMD was seen in the subsequent 6 months. Return of spontaneous menses and use of a progestin-only pill at recruitment were two potential signals that predicted a greater increase in BMD during the 6 months after exclusive lactation. CONCLUSIONS: Spine BMD increased significantly during 6 months following exclusive lactation and despite continued lactation. The factors that stimulate skeletal recovery remain to be identified.

Neither absence nor excess of FGF23 disturbs murine fetal-placental phosphorus homeostasis or prenatal skeletal development and mineralization.

Fibroblast growth factor-23 (FGF23) controls serum phosphorus largely through actions on the kidneys to excrete phosphorus and reduce calcitriol. Although these actions are well established in adults and children, the role that FGF23 plays in regulating fetal phosphorus metabolism has not been previously studied. We used several mouse models to study the effect of endogenous deficiency or excess of FGF23 on fetal phosphorus metabolism. We found that intact FGF23 does not cross the placenta from mother to fetus, but wild-type fetuses normally have intact FGF23 levels that approximately equal the maternal level. Deletion of Fgf23 or 7.8-fold higher serum FGF23 levels did not disturb any parameter of fetal mineral homeostasis, including serum and amniotic fluid phosphorus, skeletal morphology, skeletal mineral content, and placental phosphorus transport. Placentas and fetal kidneys abundantly express FGF23 target genes. Cyp24a1 was significantly reduced in Fgf23 null kidneys and was significantly increased in Phex null placentas and fetal kidneys. Phex null kidneys also showed reduced expression of Klotho. However, these changes in gene expression did not disturb any physiological parameter related to phosphorus. A 50% reduction in FGF23 also failed to affect renal phosphorus excretion into amniotic fluid when either PTH or the vitamin D receptor were absent. In conclusion, FGF23 is not an important regulator of fetal phosphorous metabolism. The active delivery of phosphorus across the placenta does not require FGF23, and that process overrides any effects that absence or excess of FGF23 might otherwise have on phosphate handling by the fetal kidneys.

Access to genetic testing and genetic counseling in vulnerable populations: the d/Deaf and hard of hearing population.

Genetic testing holds great potential for preventing morbidities and mortalities for a number of diseases through early detection and effective intervention. As the number of genetic tests expand, so will public demand for these services. Therefore, it is essential to evaluate access to genetic testing and genetic services to ensure that all Canadians, including vulnerable groups, have equitable access to all forms of health care, in keeping with the mandate of the Canadian Health Act. The purpose of this paper is to examine the literature to determine if and how the Deaf community, as a vulnerable group, is at an increased risk of inequitable access to genetic services in Canada and to discuss how those who are deaf and hard of hearing are subject to the same risks. First, we define vulnerability and describe why the Deaf community, as a social group, can be considered a vulnerable group, followed by a description of the benefits of genetic testing. Second, we describe the barriers to accessing genetic testing, and how the d/Deaf and hard of hearing population experience additional barriers. Third, we examine the difficulties incorporating genetic testing into medical practice, and how this creates additional barriers to those already at risk. Finally, we discuss the steps necessary to promote equitable access to genetic testing among the d/Deaf and hard of hearing populations within Canada, and provide recommendations for further research in this topic area. Lastly, we comment on how barriers to genetic testing vary among the d/Deaf and hard of hearing is dependent upon the type of health care system available (whether public or private).