Publications

Bone formation and remodeling involve coordinated interactions between osteoblasts and osteoclasts through signaling networks involving a variety of molecular pathways. We hypothesized that overexpression of Sonic hedgehog (Shh), a morphogen with a crucial role in skeletal development, would stimulate osteoblastogenesis and bone formation in adult animals in vivo. Systemic administration of adenovirus expressing the N-terminal form of Shh into adult mice resulted in a primary increase in osteoblasts and their precursors. Surprisingly, however, this was associated with altered trabecular morphology, decreased bone volume, and decreased compressive strength in the vertebrae. Whereas no change was detected in the number of osteoclast precursors, bone marrow stromal cells from Shh-treated mice showed enhanced osteoclastogenic potential in vitro. These effects were mediated by the PTH/PTH-related protein (PTHrP) pathway as evidenced by increased sensitivity to PTH stimulation and upregulation of the PTH/PTHrP receptor (PPR). Together, these data show that Shh has stimulatory effects on osteoprogenitors and osteoblasts in adult animals in vivo, which results in bone remodeling and reduced bone strength because of a secondary increase in osteoclastogenesis.

BACKGROUND

Data on the number of individuals eligible for screening, and rates of screening, are necessary to assess national colorectal cancer screening efforts. Such data are sparse for safety-net health systems.

METHODS

A retrospective cohort study of individuals ages 50 to 75 served by a safety-net health system in Tarrant County, TX was conducted to determine (a) the size of the potential screen-eligible population ages 50 to 75, (b) the rate of screening over 5 years among individuals ages 54 to 75, and (c) the potential predictors of screening, including sex, race/ethnicity, insurance status, frequency of outpatient visits, and socioeconomic status.

RESULTS

Of 28,708 potential screen-eligible individuals, 20,416 were ages 54 to 75 and analyzed for screening; 22.0% were screened within the preceding 5 years. Female gender, Hispanic ethnicity, ages 65 to 75, insurance status, and two or more outpatient visits were independently associated with screening. Access to care was an important factor: adjusted odds ratio, 2.57 (95% confidence interval, 2.23-2.98) for any insurance; adjusted odds ratio, 3.53 (95% confidence interval, 3.15-3.97) for two or more outpatient visits.

CONCLUSIONS

The screen-eligible population served by our safety-net health system was large, and the projected deficit in screen rates was substantial. Access to care was the dominant predictor of screening participation. If our results are replicable in similar health systems, the data suggest that screening guidelines and policy efforts must take into account the feasibility of proposed interventions. Strong advocacy for more resources for colorectal cancer screening interventions (including research into the best manner to provide screening for large populations) is needed.

Until recently, most clinical guidelines in the United States were in general agreement about the tests available for colorectal cancer screening, recommending fecal occult blood tests every year, flexible sigmoidoscopy every 5 years, both these tests together, double contrast barium enema every 5 years, or colonoscopy every 10 years. However, the release of two new sets of guidelines in 2008 has made it necessary for primary care physicians to update their knowledge of the recommended screening options. The most influential factor in determining whether a patient is screened is recommendation from a physician. The primary goal of this article is to review and critique the new guidelines for average-risk screening in adults older than 50 years. Armed with this information, primary care physicians will be better educated as to the importance of offering screening to their patients, as well as the strength and weaknesses of each recommended test.