LDL Receptor-Related Protein 5 (LRP5) Affects Bone Accrual and Eye Development

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(10)62349-5.pdf

Osteoporosis: now and the future

http://www.klinikcity.ru/wp-content/uploads/2012/03/Guidelines/Gastroenterology/Ulceral_Colitis_ACG_2010.pdf

Ulcerative colitis practice guidelines in adults: American College Of Gastroenterology, Practice Parameters Committee.

See related commentary by Kanis, page [1829][1]

Since the publication of the Osteoporosis Canada guidelines in 2002, there has been a paradigm shift in the prevention and treatment of osteoporosis and fractures. [1][2],[2][3] The focus now is on preventing fragility fractures and their negative

/pdf/2010-clinical-practice-guidelines-for-the-diagnosis-and-4ttqfkm9wl.pdf

2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary

Background Osteoporosis is a major public health problem of largely unknown cause. Loss-of-function mutations in the gene for low-density lipoprotein receptor–related protein 5 (LRP5), which acts in the Wnt signaling pathway, have been shown to cause osteoporosis–pseudoglioma. Methods We performed genetic and biochemical analyses of a kindred with an autosomal dominant syndrome characterized by high bone density, a wide and deep mandible, and torus palatinus. Results Genetic analysis revealed linkage of the syndrome to chromosome 11q12–13 (odds of linkage, >1 million to 1), an interval that contains LRP5. Affected members of the kindred had a mutation in this gene, with valine substituted for glycine at codon 171 (LRP5V171 ). This mutation segregated with the trait in the family and was absent in control subjects. The normal glycine lies in a so-called propeller motif that is highly conserved from fruit flies to humans. Markers of bone resorption were normal in the affected subjects, whereas markers of bo...

High Bone Density Due to a Mutation in LDL-Receptor–Related Protein 5

OBJECTIVES\nTo clarify the factors associated with prevention, diagnosis, and treatment of osteoporosis, and to present the most recent information available in these areas.\n\n\nPARTICIPANTS\nFrom March 27-29, 2000, a nonfederal, nonadvocate, 13-member panel was convened, representing the fields of internal medicine, family and community medicine, endocrinology, epidemiology, orthopedic surgery, gerontology, rheumatology, obstetrics and gynecology, preventive medicine, and cell biology. Thirty-two experts from these fields presented data to the panel and an audience of 699. Primary sponsors were the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institutes of Health Office of Medical Applications of Research.\n\n\nEVIDENCE\nMEDLINE was searched for January 1995 through December 1999, and a bibliography of 2449 references provided to the panel. Experts prepared abstracts for presentations with relevant literature citations. Scientific evidence was given precedence over anecdotal experience.\n\n\nCONSENSUS PROCESS\nThe panel, answering predefined questions, developed conclusions based on evidence presented in open forum and the literature. The panel composed a draft statement, which was read and circulated to the experts and the audience for public discussion. The panel resolved conflicts and released a revised statement at the end of the conference. The draft statement was posted on the Web on March 30, 2000, and updated with the panel's final revisions within a few weeks.\n\n\nCONCLUSIONS\nThough prevalent in white postmenopausal women, osteoporosis occurs in all populations and at all ages and has significant physical, psychosocial, and financial consequences. Risks for osteoporosis (reflected by low bone mineral density [BMD]) and for fracture overlap but are not identical. More attention should be paid to skeletal health in persons with conditions associated with secondary osteoporosis. Clinical risk factors have an important but poorly validated role in determining who should have BMD measurement, in assessing fracture risk, and in determining who should be treated. Adequate calcium and vitamin D intake is crucial to develop optimal peak bone mass and to preserve bone mass throughout life. Supplementation with these 2 nutrients may be necessary in persons not achieving recommended dietary intake. Gonadal steroids are important determinants of peak and lifetime bone mass in men, women, and children. Regular exercise, especially resistance and high-impact activities, contributes to development of high peak bone mass and may reduce risk of falls in older persons. Assessment of bone mass, identification of fracture risk, and determination of who should be treated are the optimal goals when evaluating patients for osteoporosis. Fracture prevention is the primary treatment goal for patients with osteoporosis. Several treatments have been shown to reduce the risk of osteoporotic fractures, including those that enhance bone mass and reduce the risk or consequences of falls. Adults with vertebral, rib, hip, or distal forearm fractures should be evaluated for osteoporosis and given appropriate therapy.

Lou Glasse

Papers

Osteoporosis prevention, diagnosis, and therapy