Population-level risks of physical activity: Saving bones and screening hearts

Documented risks of physical activity include reduced bone mineral density at high activity volume, and sudden cardiac death among adults and adolescents. Further illumination of these risks is needed to inform future public health guidelines. The present research seeks to 1) quantify the association between physical activity and bone mineral density (BMD) across a broad range of activity volume, 2) assess the utility of an existing pre-screening questionnaire among US adults, and 3) determine if pre-screening risk stratification by questionnaire predicts referral to physician among Texas adolescents. ^ Among 9,468 adults 20 years of age or older in the National Health and Nutrition Examination Survey (NHANES) 2007-2010, linear regression analyses revealed generally higher BMD at the lumbar spine and proximal femur with greater reported activity volume. Only lumbar BMD in women was unassociated with activity volume. Among men, BMD was similar at activity beyond four times the minimum volume recommended in the Physical Activity Guidelines. These results suggest that the range of activity reported by US adults is not associated with low BMD at either site. ^ The American Heart Association / American College of Sports Medicine Preparticipation Questionnaire (AAPQ) was applied to 6,661 adults 40 years of age or older from NHANES 2001-2004 by using NHANES responses to complete AAPQ items. Following AAPQ referral criteria, 95.5% of women and 93.5% of men would be referred to a physician before exercise initiation, suggesting little utility for the AAPQ among adults aged 40 years or older. Unnecessary referral before exercise initiation may present a barrier to exercise adoption and may strain an already stressed healthcare infrastructure. ^ Among 3181 athletes in the Texas Adolescent Athlete Heart Screening Registry, 55.2% of boys and 62.2% of girls were classified as high-risk based on questionnaire answers. Using sex-stratified contingency table analyses, risk categories were not significantly associated with referral to physician based on electrocardiogram or echocardiogram, nor were they associated with confirmed diagnoses on follow-up. Additional research is needed to identify which symptoms are most closely related to sudden cardiac death, and determine the best methods for rapid and reliable assessment. ^ In conclusion, this research suggests that the volume of activity reported by US adults is not associated with low BMD at two clinically relevant sites, casts doubts on the utility of two existing cardiac screening tools, and raises concern about barriers to activity erected through ineffective screening. These findings augment existing research in this area that may inform revisions to the Physical Activity Guidelines regarding risk mitigation.^

New insights into the role of the duodenal vitamin D receptor in calcium homeostasis

It is generally believed that 1,25(OH)2D3, bound to its receptor (VDR) contributes to calcium homeostasis by regulating active calcium absorption in the proximal small intestine. However, studying patients with hereditary vitamin D-resistant rickets (HVDRR) provided investigators with a better understanding of VDR's role in calcium homeostasis. HVDRR patients have inactivating mutations in the VDR, and as a consequence they develop hypocalcemia, hyperparathyroidism and severe rickets. However, these phenotypes can be corrected if the patients are given IV infusions of calcium or dietary calcium. This raises the question of what is the physiological significance of VDR-regulated active calcium absorption if calcium homeostasis can be restored independently of the VDR. ^ In order to distinguish the contribution of VDR in the proximal small intestine to overall calcium homeostasis, I generated transgenic mice expressing the human VDR (hVDR) exclusively in the proximal small intestine of mVDR-/- mice by using an hVDR-expressing transgene driven by the duodenal-specific adenosine deaminase enhancer (hVDR+/mVDR-/-). hVDR+/mVDR-/- mice expressed transcriptionally active hVDR only in the proximal small intestine and responded to 1,25(OH)2D3 by up-regulating expression of TRPV6 and calbindin D9K, genes involved in calcium absorption. Furthermore, ligated duodenal loop assays determined that calcium absorption in hVDR+/mVDR-/- mice was as responsive to 1,25(OH)2D3 as in WT mice. Despite having a functional hVDR in the proximal small intestine, hVDR+/mVDR-/- mice were hypocalcemic, had hyperparathyroidism, and were rachitic when fed a normal rodent diet at weaning, as were the mVDR-/- mice. However, when fed a high calcium, phosphorus, and lactose diet (rescue diet), the hVDR+/mVDR-/- mice responded more effectively than the mVDR-/- mice by down-regulation of parathyroid hormone production and by a greater increase in bone mineralization. Furthermore, when three-month-old rachitic mice were fed a rescue diet for 3 weeks, serum calcium and bone mineral content were normalized in hVDR+/mVDR-/- mice, but not in mVDR-/- mice. ^ In conclusion, hVDR expression enabled young mice to better use the rescue diet than mVDR-/- mice. Expression of transgenic hVDR also protected the ability of older mice to respond to the rescue diet despite the absence of the VDR elsewhere in the intestinal tract. I propose that because hVDR+/mVDR-/- mice responded better than mVDR-/- mice to the rescue diet, it is likely that VDR expression in the proximal small intestine is necessary in nutritional (insufficient dietary calcium) and physiological (age) conditions when passive calcium absorption is inadequate. ^