PAGET’S DISEASE OF THE BONE: AN UNUSUAL CAUSE OF LOW BACK PAIN IN AN ADULT MALE

Paget's disease of bone (PDB) affects up to 1% of people of European origin aged 55 years and above. It is characterized by focal abnormalities of bone remodelling which disrupt normal bone architecture, leading to expansion and reduced mechanical strength of affected bones. This can lead to various complications including deformity, fracture, nerve compression syndromes, and osteoarthritis, although many patients are asymptomatic. Genetic factors play a key role in the pathogenesis of PDB. This seems to be mediated by a combination of rare genetic variants which cause familial forms of the disease and common variants which increase susceptibility to environmental triggers. Environmental factors which have been suggested to predispose to PDB include viral infections, calcium and vitamin D deficiency, and excessive mechanical loading of affected bones. The diagnosis can be made by the characteristic changes seen on radiographs, but isotope bone scans are helpful in defining disease extent. Serum alkaline phosphatase levels can be used as a measure of disease activity. Inhibitors of bone resorption are the mainstay of medical management for PDB and bisphosphonates are regarded as the treatment of choice. Bisphosphonates are highly effective at reducing bone turnover in PDB and have been found to heal osteolytic lesions, and normalize bone histology. Although bisphosphonates can improving bone pain caused by elevated bone turnover, most patients require additional therapy to deal with symptoms associated with disease complications. It is currently unclear whether bisphosphonate therapy is effective at preventing complications of PDB.

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Juvenile Paget’s disease: Report of a family with a novel missense mutation and unique radiological manifestations in a heterozygote

QJM ◽

10.1093/qjmed/hcaa063.022a ◽

2020 ◽

Vol 113 (Supplement_1) ◽

Author(s):

O Khalifa ◽

K Ramzan ◽

A S Moustafa ◽

K AlMane ◽

M Abdelfattah ◽

...

Keyword(s):

Alkaline Phosphatase ◽

Bone Turnover ◽

Skeletal Dysplasia ◽

Serum Alkaline Phosphatase ◽

Phenotypic Variability ◽

Paget’S Disease ◽

Paget's Disease ◽

Homozygous Mutation ◽

Markers Of Bone Turnover ◽

Juvenile Paget’S Disease

Abstract Juvenile Paget’s disease (JPD) is a rare, generalized skeletal disorder characterized by markedly increased bone turnover secondary to enhanced osteoclastic activity. The patients with JPD develop progressive, widespread skeletal involvement and non-skeletal manifestations. Objectives To identify the characteristic molecular, biochemical, radiological, and audiological findings in three siblings with JPD associated with intrafamilial phenotypic variability. Patients and Methods A Saudi family with 3 affected siblings was recruited. Biochemical measurement of serum alkaline phosphatase and markers of bone turnover were performed. Genetic testing and sequencing of a panel of 22 known genes for skeletal dysplasia with increase bone density were performed by next generation sequencing (NGS). Radiological and audiological assessment were also performed. Results Patients showed marked elevation of serum alkaline phosphatase and markers of bone turnover. A novel homozygous mutation c.433T>G (p.Cys145Gly) in exon 3 of TNFRSF11B gene was identified in the 3 affected siblings. Both parents were heterozygous for the mutation. The heterozygote father had thickening of calvarium, a radiological manifestation of JPD. The eldest child (index case) had a unique striking distortion of the skull bones as evidenced by 3-D computed tomography of skull. He had also bilateral inner ear structural deformity and severe sensorineural hearing loss. Conclusions: JPD is a rare disorder that can be highly overlooked due to phenotypic overlap with other disorders of skeletal dysplasia. Mutations affecting cysteine residues result in the most severe JPD phenotypes. NGS is useful for early diagnosis of JPD, a prerequisite for successful treatment strategy.

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Paget’s disease of bone

Oxford Textbook of Rheumatology ◽

10.1093/med/9780199642489.003.0144_update_002 ◽

2013 ◽

pp. 1237-1244

Author(s):

Stuart H. Ralston

Keyword(s):

Bone Turnover ◽

Viral Infections ◽

Serum Alkaline Phosphatase ◽

Paget’S Disease ◽

Paget's Disease ◽

Paget’S Disease Of Bone ◽

Bone Architecture ◽

Paget's Disease Of Bone ◽

Disease Extent ◽

Bone Scans

Paget’s disease of bone (PDB) affects up to 1% of people of European origin aged 55 years and above. It is characterized by focal abnormalities of bone remodelling which disrupt normal bone architecture, leading to expansion and reduced mechanical strength of affected bones. This can lead to various complications including deformity, fracture, nerve compression syndromes, and osteoarthritis, although many patients are asymptomatic. Genetic factors play a key role in the pathogenesis of PDB. This seems to be mediated by a combination of rare genetic variants which cause familial forms of the disease and common variants which increase susceptibility to environmental triggers. Environmental factors which have been suggested to predispose to PDB include viral infections, calcium and vitamin D deficiency, and excessive mechanical loading of affected bones. The diagnosis can be made by the characteristic changes seen on radiographs, but isotope bone scans are helpful in defining disease extent. Serum alkaline phosphatase levels can be used as a measure of disease activity. Inhibitors of bone resorption are the mainstay of medical management for PDB and bisphosphonates are regarded as the treatment of choice. Bisphosphonates are highly effective at reducing bone turnover in PDB and have been found to heal osteolytic lesions, and normalize bone histology. Although bisphosphonates can improving bone pain caused by elevated bone turnover, most patients require additional therapy to deal with symptoms associated with disease complications. It is currently unclear whether bisphosphonate therapy is effective at preventing complications of PDB.

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Paget’s disease of bone

10.1093/med/9780199642489.003.0144_update_001 ◽

2016 ◽

Author(s):

Stuart H. Ralston

Keyword(s):

Bone Turnover ◽

Viral Infections ◽

Serum Alkaline Phosphatase ◽

Paget’S Disease ◽

Paget's Disease ◽

Bisphosphonate Therapy ◽

Paget’S Disease Of Bone ◽

Bone Architecture ◽

Paget's Disease Of Bone ◽

Disease Extent

Paget’s disease of bone (PDB) affects up to 1% of people of European origin aged 55 years and above. It is characterized by focal abnormalities of bone remodelling which disrupt normal bone architecture, leading to expansion and reduced mechanical strength of affected bones. This can lead to various complications including deformity, fracture, nerve compression syndromes, and osteoarthritis, although many patients are asymptomatic. Genetic factors play a key role in the pathogenesis of PDB. This seems to be mediated by a combination of rare genetic variants which cause familial forms of the disease and common variants which increase susceptibility to environmental triggers. Environmental factors which have been suggested to predispose to PDB include viral infections, calcium and vitamin D deficiency, and excessive mechanical loading of affected bones. The diagnosis can be made by the characteristic changes seen on radiographs, but isotope bone scans are helpful in defining disease extent. Serum alkaline phosphatase levels can be used as a measure of disease activity. Inhibitors of bone resorption are the mainstay of medical management for PDB and bisphosphonates are regarded as the treatment of choice. Bisphosphonates are highly effective at reducing bone turnover in PDB and have been found to heal osteolytic lesions, and normalize bone histology. Although bisphosphonates can improving bone pain caused by elevated bone turnover, most patients require additional therapy to deal with symptoms associated with disease complications. It is currently unclear whether bisphosphonate therapy is effective at preventing complications of PDB.

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The Effect of Zoledronic Acid on Serum Biomarkers among Patients with Chronic Low Back Pain and Modic Changes in Lumbar Magnetic Resonance Imaging

Diagnostics ◽

10.3390/diagnostics9040212 ◽

2019 ◽

Vol 9 (4) ◽

pp. 212 ◽

Cited By ~ 2

Author(s):

Katri Koivisto ◽

Jaro Karppinen ◽

Marianne Haapea ◽

Jyri Järvinen ◽

Eero Kyllönen ◽

...

Keyword(s):

Low Back Pain ◽

Back Pain ◽

Zoledronic Acid ◽

Bone Turnover ◽

Chronic Low Back Pain ◽

Placebo Treatment ◽

Serum Biomarkers ◽

Modic Changes ◽

Low Back ◽

One Year

The aim of the current study was to compare changes in serum biomarkers, including inflammatory mediators, signaling molecules, growth factors and markers of bone turnover after a single intravenous infusion of 5 mg zoledronic acid (ZA, a long-acting bisphosphonate; n = 20) or placebo (n = 20) among patients with Modic changes (MC) and chronic low back pain in a randomized controlled design. The MCs were classified into M1, predominating M1, predominating M2, and M2. We measured the serum concentrations of 39 biomarkers at baseline, and one month and one year after treatment. After Benjamini–Hochberg (B–H) correction, we observed significant differences in three biomarkers over one year: Interferon-γ-inducible protein (IP-10) had risen in the ZA group (p = 0.005), whereas alkaline phosphatase (AFOS) and intact procollagen I N-terminal propeptide (iPINP) had significantly decreased in the ZA group, but had not changed in the placebo group (p < 0.001 for both). Change in iPINP correlated with change in the volume of all MC and M1 lesions. ZA downregulated bone turnover markers as expected and, surprisingly, increased the chemokine IP-10 relative to placebo treatment. This adds to our knowledge of the effects of ZA on MC and the biomarkers that signal this process.

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