Incidence and Natural History of Paget's Disease of Bone in England and Wales

Staa, Tjeerd van; Selby, Peter L.; Leufkens, Hubert G. M.; Lyles, Kenneth W.; Sprafka, J. Michael; Cooper, Cyrus

doi:10.1359/jbmr.2002.17.3.465

Cited by 317 publications

(235 citation statements)

References 22 publications

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“…However, despite the bowing and cracking, the overall fracture risk to patients is low, and fracture events at pathological skeletal sites are uncommon (occurring in B2% of patients). 73,74 For Paget's disease to produce the marked changes in bone's mechanical integrity (that is, bowing and deformities) at the macroscale, the disease must be changing the bone structure and in turn the mechanical mechanisms through which the bone resists deformation and fracture. Indeed, the overall mineral content is significantly lower in Paget's disease, which has also a greater heterogeneity of mineralized bone packets (Figure 8a-c).…”

Section: Paget's Disease Of Bone (Pdb)mentioning

confidence: 99%

The fracture mechanics of human bone: influence of disease and treatment

2015

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Aging and bone diseases are associated with increased fracture risk. It is therefore pertinent to seek an understanding of the origins of such disease-related deterioration in bone's mechanical properties. The mechanical integrity of bone derives from its hierarchical structure, which in healthy tissue is able to resist complex physiological loading patterns and tolerate damage. Indeed, the mechanisms through which bone derives its mechanical properties make fracture mechanics an ideal framework to study bone's mechanical resistance, where crack-growth resistance curves give a measure of the intrinsic resistance to the initiation of cracks and the extrinsic resistance to the growth of cracks. Recent research on healthy cortical bone has demonstrated how this hierarchical structure can develop intrinsic toughness at the collagen fibril scale mainly through sliding and sacrificial bonding mechanisms that promote plasticity. Furthermore, the bone-matrix structure develops extrinsic toughness at much larger micrometer length-scales, where the structural features are large enough to resist crack growth through crack-tip shielding mechanisms. Although healthy bone tissue can generally resist physiological loading environments, certain conditions such as aging and disease can significantly increase fracture risk. In simple terms, the reduced mechanical integrity originates from alterations to the hierarchical structure. Here, we review how human cortical bone resists fracture in healthy bone and how changes to the bone structure due to aging, osteoporosis, vitamin D deficiency and Paget's disease can affect the mechanical integrity of bone tissue.

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Section: Paget's Disease Of Bone (Pdb)mentioning

confidence: 99%

The fracture mechanics of human bone: influence of disease and treatment

2015

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“…(1)(2)(3)(4)(5)(6)(7)(8)(9) The typical features are focal lesions where the bone remodeling process is accelerated, leading to a disorganized bone matrix. Consequently, symptoms such as bone pain, skeletal deformities, fractures, secondary osteoarthritis, deafness, and neurologic complications are observed.…”

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confidence: 99%

Genetic variation in the TNFRSF11A gene encoding RANK is associated with susceptibility to Paget's disease of bone

Chung

Beyens

Riches

et al. 2010

Journal of Bone and Mineral Research

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RANK (receptor activator of nuclear factor-kB), encoded by TNFRSF11A, is a key protein in osteoclastogenesis. TNFRSF11A mutations cause Paget's disease of bone (PDB)-like diseases (ie, familial expansile osteolysis, expansile skeletal hyperphosphatasia, and early-onset PDB) and an osteoclast-poor form of osteopetrosis. However, no TNFRSF11A mutations have been found in classic PDB, neither in familial nor in isolated cases. To investigate the possible relationship between TNFRSF11A polymorphisms and sporadic PDB, we conducted an association study including 32 single-nucleotide polymorphisms (SNPs) in 196 Belgian sporadic PDB patients and 212 control individuals. Thirteen SNPs and 3 multimarker tests (MMTs) turned out to have a p value of between .036 and 3.17 Â 10 À4 , with the major effect coming from females. Moreover, 6 SNPs and 1 MMT withstood the Bonferroni correction ( p < .002). Replication studies were performed for 2 nonsynonymous SNPs (rs35211496 and rs1805034) in a Dutch and a British cohort. Interestingly, both SNPs resulted in p values ranging from .013 to 8.38 Â 10 À5 in both populations. Meta-analysis over three populations resulted in p ¼ .002 for rs35211496 and p ¼ 1.27 Â 10 À8 for rs1805034, again mainly coming from the female subgroups. In an attempt to identify the underlying causative SNP, we performed functional studies for the coding SNPs as well as resequencing efforts of a 31-kb region harboring a risk haplotype within the Belgian females. However, neither approach resulted in significant evidence for the causality of any of the tested genetic variants. Therefore, further studies are needed to identify the real cause of the increased risk to develop PDB shown to be present within TNFRSF11A. ß

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“…It is a focal skeletal disorder characterized by an accelerated bone turnover 210. The incidence of Paget disease is difficult to estimate because most patients are asymptomatic 1–310. The incidence appears to increase with age, and there seems to be a slight male preponderance 11.…”

Section: Discussionmentioning

confidence: 99%

“…The incidence appears to increase with age, and there seems to be a slight male preponderance 11. The disease is most common in nations with a large Anglo-Saxon population but is considered rare in other parts of the world 34. In Saudi Arabia, little information has been published about this disease.…”

Section: Discussionmentioning

confidence: 99%

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Paget disease of the bone: Does it exist in Saudi Arabia?

Alshaikh

Almanea

Alzahrani

2011

Annals of Saudi Medicine

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Paget disease of the bone is a chronic disease characterized by accelerated bone turnover with abnormal repair leading to expansion, pain and deformities. The disease is common in the West, but little if any information is available on its existence in the Arab world, including Saudi Arabia. We present four cases of Saudi patients with Paget disease with variable presentations. The first case, a 63-year-old woman with a history of papillary thyroid cancer, presented with bone, shoulder and chest wall pain and foci of uptake in the ribs and skull that were thought to be metastases, indicating the possibility of diagnostic difficulty in a patient with history of malignancy. Bone biopsy confirmed the diagnosis of Paget disease. The second case was a 47-year-old asymptomatic woman with an elevated alkaline phosphatase of 427 U/L, a common presentation but at an unusual age. Plain x-rays and bone scan confirmed the diagnosis. The third case was a 43-year-old man who presented with hearing impairment and right knee osteoarthritis, unusual presentations at a young age leading to a delay in diagnosis. The fourth case was a 45-year-old man who presented with sacroiliac pain and normal biochemical values, including a normal alkaline phosphatase. Bone biopsy unexpectedly revealed features of Paget disease, which evolved over time into a classical form. A common feature in all except the first case was the relatively young age. Paget disease does exist in Saudi Arabia, and it should be considered in the differential diagnosis of similar cases.

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Incidence and Natural History of Paget's Disease of Bone in England and Wales

Cited by 317 publications

References 22 publications

The fracture mechanics of human bone: influence of disease and treatment

The fracture mechanics of human bone: influence of disease and treatment

Genetic variation in the TNFRSF11A gene encoding RANK is associated with susceptibility to Paget's disease of bone

Paget disease of the bone: Does it exist in Saudi Arabia?

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