Risk factors for stress fracture among young female cross-country runners.

PURPOSE: To identify risk factors for stress fracture among young female distance runners. METHODS: Participants were 127 competitive female distance runners, aged 18-26, who provided at least some follow-up data in a randomized trial among 150 runners of the effects of oral contraceptives on bone health. After completing a baseline questionnaire and undergoing bone densitometry, they were followed an average of 1.85 yr. RESULTS: Eighteen participants had at least one stress fracture during follow-up. Baseline characteristics associated (P<0.10) in multivariate analysis with stress fracture occurrence were one or more previous stress fractures (rate ratio [RR] [95% confidence interval]=6.42 (1.80-22.87), lower whole-body bone mineral content (RR=2.70 [1.26-5.88] per 1-SD [293.2 g] decrease), younger chronologic age (RR=1.42 [1.05-1.92] per 1-yr decrease), lower dietary calcium intake (RR=1.11 [0.98-1.25] per 100-mg decrease), and younger age at menarche (RR=1.92 [1.15-3.23] per 1-yr decrease). Although not statistically significant, a history of irregular menstrual periods was also associated with increased risk (RR=3.41 [0.69-16.91]). Training-related factors did not affect risk. CONCLUSION: The results of this and other studies indicate that risk factors for stress fracture among young female runners include previous stress fractures, lower bone mass, and, although not statistically significant in this study, menstrual irregularity. More study is needed of the associations between stress fracture and age, calcium intake, and age at menarche. Given the importance of stress fractures to runners, identifying preventive measures is of high priority.

The effect of oral contraceptives on bone mass and stress fractures in female runners.

PURPOSE: To determine the effect of oral contraceptives (OC) on bone mass and stress fracture incidence in young female distance runners. METHODS: One hundred fifty competitive female runners ages 18-26 yr were randomly assigned to OC (30 microg of ethinyl estradiol and 0.3 mg of norgestrel) or control (no intervention) for 2 yr. Bone mineral density (BMD) and content (BMC) were measured yearly by dual x-ray absorptiometry. Stress fractures were confirmed by x-ray, magnetic resonance imaging, or bone scan. RESULTS: Randomization to OC was unrelated to changes in BMD or BMC in oligo/amenorrheic (N=50) or eumenorrheic runners (N=100). However, treatment-received analyses (which considered actual OC use) showed that oligo/amenorrheic runners who used OC gained about 1% per year in spine BMD (P<0.005) and whole-body BMC (P<0.005), amounts similar to those for runners who regained periods spontaneously and significantly greater than those for runners who remained oligo/amenorrheic (P<0.05). Dietary calcium intake and weight gain independently predicted bone mass gains in oligo/amenorrheic runners. Randomization to OC was not significantly related to stress fracture incidence, but the direction of the effect was protective in both menstrual groups (hazard ratio [95% CI]: 0.57 [0.18, 1.83]), and the effect became stronger in treatment-received analyses. The trial's statistical power was reduced by higher-than-anticipated noncompliance. CONCLUSION: OC may reduce the risk for stress fractures in female runners, but our data are inconclusive. Oligo/amenorrheic athletes with low bone mass should be advised to increase dietary calcium and take steps to resume normal menses, including weight gain; they may benefit from OC, but the evidence is inconclusive.

Increased falling as a risk factor for fracture among older women: the study of osteoporotic fractures.

More frequent falling is associated with a higher risk of fracture among older women, but it is not known whether an increased rate of falling, independent of the average rate, also increases fracture risk. The authors examined the relation between an increase in the rate of falls during the first 4 years of follow-up and the subsequent fracture rate, reported for a median of 6.3 years (1986-1998), in 9,106 US women aged 65 years or more. Women in the upper quartile of increasing falls (>0.44 falls/year/year) had greater risks of subsequent hip fracture (rate ratio = 1.42, 95% confidence interval: 0.99, 2.04) and fracture of the proximal humerus (rate ratio = 1.79, 95% confidence interval: 1.08, 2.95) than women without an increase in falls, after adjustment for age, average rate of falls over 4 years, and known risk factors for fracture. Risks of distal forearm, ankle, or foot fracture were not elevated. The associations between fracture risk and increasing falls were not accounted for by baseline physical or cognitive function. An increase in the rate of falls, independent of the average rate, may be associated with a higher risk of frailty (hip and proximal humerus) fractures but not fractures at other sites.

Urine testing in methadone maintenance treatment: applications and limitations.

We consider here the applications and limitations of urine testing schedules used in methadone maintenance treatment programs. We show that for patients attending clinic daily, any practical testing schedule will only reliably detect those who are using heroin or other illicit drugs very frequently (e.g., daily). For patients with take-home privileges no testing schedule can effectively detect either skipped doses or use of illicit drugs. Consequently, whether for patients attending clinic daily or for patients with take-home privileges, some programs, as measured by urine test results, may actually be less successful than they appear to be.

Disordered eating, menstrual irregularity, and bone mineral density in female runners.

PURPOSE: To examine the relationships between disordered eating, menstrual irregularity, and low bone mineral density (BMD) in young female runners. METHODS: Subjects were 91 competitive female distance runners aged 18-26 yr. Disordered eating was measured by the Eating Disorder Inventory (EDI). Menstrual irregularity was defined as oligo/amenorrhea (0-9 menses per year). BMD was measured by dual x-ray absorptiometry. RESULTS: An elevated score on the EDI (highest quartile) was associated with oligo/amenorrhea, after adjusting for percent body fat, age, miles run per week, age at menarche, and dietary fat, (OR [95% CI]: 4.6 [1.1-18.6]). Oligo/amenorrheic runners had lower BMD than eumenorrheic runners at the spine (-5%), hip (-6%), and whole body (-3%), even after accounting for weight, percent body fat, EDI score, and age at menarche. Eumenorrheic runners with elevated EDI scores had lower BMD than eumenorrheic runners with normal EDI scores at the spine (-11%), with trends at the hip (-5%), and whole body (-5%), after adjusting for differences in weight and percent body fat. Runners with both an elevated EDI score and oligo/amenorrhea had no further reduction in BMD than runners with only one of these risk factors. CONCLUSION: In young competitive female distance runners, (i) disordered eating is strongly related to menstrual irregularity, (ii) menstrual irregularity is associated with low BMD, and (iii) disordered eating is associated with low BMD in the absence of menstrual irregularity.

A phase II, double-blind, randomized, placebo-controlled clinical trial of tgAAVCF using maxillary sinus delivery in patients with cystic fibrosis with antrostomies.

tgAAVCF, an adeno-associated cystic fibrosis transmembrane conductance regulator (CFTR) viral vector/gene construct, was administered to 23 patients in a Phase II, double-blind, randomized, placebo-controlled clinical trial. For each patient, a dose of 100,000 replication units of tgAAVCF was administered to one maxillary sinus, while the contralateral maxillary sinus received a placebo treatment, thereby establishing an inpatient control. Neither the primary efficacy endpoint, defined as the rate of relapse of clinically defined, endoscopically diagnosed recurrent sinusitis, nor several secondary endpoints (sinus transepithelial potential difference [TEPD], histopathology, sinus fluid interleukin [IL]-8 measurements) achieved statistical significance when comparing treated to control sinuses within patients. One secondary endpoint, measurements of the anti-inflammatory cytokine IL-10 in sinus fluid, was significantly (p < 0.03) increased in the tgAAVCF-treated sinus relative to the placebo-treated sinus at day 90 after vector instillation. The tgAAVCF administration was well tolerated, without adverse respiratory events, and there was no evidence of enhanced inflammation in sinus histopathology or alterations in serum-neutralizing antibody titer to adeno-associated virus (AAV) capsid protein after vector administration. In summary, this Phase II trial confirms the safety of tgAAVCF but provides little support of its efficacy in the within-patient controlled sinus study. Various potentially confounding factors are discussed.