The information in this Seminar is based on MEDLINE and PubMed searches with the search terms “osteoporosis” or “fracture” in combination with the keywords “calcium”, “vitamin D”, “bisphosphonates”, “selective estrogen receptor modulator”, “parathyroid hormone”, “strontium”, “RANKL”, “Receptors-LDL” or terms such as “randomized trials” or “meta-analyses”. We mainly selected papers from the past 5 years, but also included frequently referenced and highly regarded older papers. Some review
SeminarOsteoporosis
Section snippets
Epidemiology
Osteoporosis is a skeletal disease characterised by low bone mass and microarchitectural deterioration with a resulting increase in bone fragility and hence susceptibility to fracture.1 It is an important public health issue because of the potentially devastating results2 and high cumulative rate of fractures; in white populations, about 50% of women and 20% of men older than 50 years will have a fragility fracture in their remaining lifetime.3 Indeed, in white women, the one in six lifetime
Pathophysiology
Osteoporotic fractures result from a combination of reduced bone strength and increased rate of falls. Although bone mineral density remains the best available non-invasive assessment of bone strength in routine clinical practice, many other skeletal characteristics also contribute to bone strength. These include bone macroarchitecture (shape and geometry), bone microarchitecture (both trabecular and cortical), matrix and mineral composition, as well as the degree of mineralisation, microdamage
Assessment of fracture risk
Since 1994, the benchmark for diagnosis of osteoporosis has been the assessment of bone mineral density. The ability to predict fracture risk from this measure is at least as good as if not better than the ability to predict heart disease risk from blood cholesterol concentrations and to predict stroke risk from blood pressure values.37 However, low bone mineral density alone does not mean an individual will have a fracture, and although the widely accepted diagnostic threshold of a T score
Management
Since most fractures happen as a result of falls, attention to reducing the risk of falls seems important. Although no studies are available that show that strategies to reduce the rate of falls will reduce fractures, the use of hip protectors to reduce the impact of falls has proven effective in high-risk individuals,41 although compliance remains an issue.42 At a mechanistic level, drugs can be considered in terms of whether they act mainly on bone resorption (antiresorptive agents) or on
Search strategy and selection criteria
References (98)
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Epidemiology and outcomes of osteoporotic fractures
Lancet
(2002) - et al.
Magnitude and impact of osteoporosis and fractures
- et al.
Epidemiology of fractures in England and Wales
Bone
(2001) - et al.
A meta-analysis of previous fracture and subsequent fracture risk
Bone
(2004) - et al.
Mortality after all major types of osteoporotic fracture in men and women: an observational study
Lancet
(1999) - et al.
Prenatal and childhood influences on osteoporosis
Best Pract Res Clin Endocrinol Metab
(2002) - et al.
Gain in bone mineral mass in prepubertal girls 3.5 years after discontinuation of calcium supplementation: a follow-up study
Lancet
(2001) - et al.
The effects of estrogen on osteoprotegerin, RANKL, and estrogen receptor expression in human osteoblasts
Bone
(2003) - et al.
A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait
Am J Hum Genet
(2002) - et al.
LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development
Cell
(2001)
LRP5 gene polymorphisms predict bone mass and incident fractures in elderly Australian women
Bone
Sclerostin binds to LRP5/6 and antagonises canonical Wnt signalling
J Biol Chem
SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor
J Biol Chem
Polymorphisms in the sclerosteosis/van Buchem disease gene (SOST) region are associated with bone-mineral density in elderly white
Am J Hum Genet
Prevention of falls and consequent injuries in elderly people
Lancet
Long-term effects of calcium supplementation on bone loss and fractures in postmenopausal women: a randomized controlled trial
Am J Med
Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures
Lancet
Four-year study of intermittent cyclic etidronate treatment of postmenopausal osteoporosis - three years of blinded therapy followed by one year of open therapy
Am J Med
Long-term efficacy of risedronate: a 5-year placebo-controlled clinical experience
Bone
Pamidronate (Aredia) and zolendronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic
J Oral Maxillofac Surg
Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases
J Oral Maxillofac Surg
Severity of prevalent vertebral fractures and the risk of subsequent vertebral and nonvertebral fractures: results from the MORE trial
Bone
What PROOF proves about calcitonin and clinical trials
Am J Med
Bone health and osteoporosis: a report of the Surgeon-General
The socioeconomic burden of fractures: today and in the 21st century
Am J Med
Incidence of vertebral fracture in Europe: results from the European Prospective Osteoporosis Study (EPOS)
J Bone Miner Res
Incidence of clinically diagnosed vertebral fractures: a population-based study in Rochester, Minnesota, 1985–1989
J Bone Miner Res
Pre-existing fractures and bone mass predict vertebral fracture incidence in women
Ann Intern Med
Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis
J Bone Miner Res
Vertebral fractures predict subsequent fractures
Osteoporos Int
Remodeling and skeletal fragility
Osteoporos Int
Role of collagen and other organics in the mechanical properties of bone
Osteoporos Int
Pathophysiology of osteoporosis
Gender differences in the genetic factors responsible for variation in bone density and ultrasound
J Bone Miner Res
Vitamin D receptor gene polymorphisms and the risk of fractures in older women
J Bone Miner Res
Association of collagen Ialpha 1 Sp1 polymorphism with the risk of prevalent fractures: a meta-analysis
J Bone Miner Res
A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality
J Clin Invest
Estrogen, cytokines and pathogenesis of postmenopausal osteoporosis
J Bone Miner Res
Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-α
J Clin Invest
Changes in proinflammatory cytokine activity after menopause
Endocr Rev
Estrogen promotes apoptosis of murine osteoclasts mediated by TGF-β
Nat Med
Osteoclast differentiation and activation
Nature
High bone density due to a mutation in LDL-receptor related protein 5
N Engl J Med
Influence of LRP5 polymorphisms on normal variation in BMD
J Bone Miner Res
Genomic deletion of a long range bone enhancer misregulates sclerostin in Van Buchem disease
Genome Res
Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures
BMJ
Assessment of fracture risk
Osteoporos Int
Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: the OFELY study
J Bone Miner Res
Biochemical indices of bone turnover and the assessment of fracture probability
Osteoporos Int
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