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Osteoporosis International : a Journal... Jul 2015The aim of this systematic review and meta-analysis is to study the utility of the commonly used bone turnover markers in evaluating disease activity in patients with... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
The aim of this systematic review and meta-analysis is to study the utility of the commonly used bone turnover markers in evaluating disease activity in patients with Paget's disease of bone before and after treatment with bisphosphonates. We found good correlation between the bone turnover marker concentrations and disease activity assessed by bone scintigraphy.
INTRODUCTION
Paget's disease of bone is a common skeletal disorder of the elderly. Bone turnover marker concentrations are used for diagnosis and follow-up. We aimed to compare the available bone turnover markers and determine their utility in assessing disease activity when compared to quantitative bone scintigraphy.
METHODS
We conducted a systematic review and meta-analysis searching MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus. We evaluated total alkaline phosphatase (total ALP), bone-specific alkaline phosphatase (bone ALP), procollagen type 1 amino-terminal propeptide (P1NP), serum, and urine C-terminal telopeptide (uCTx and sCTx, respectively), and urine N-terminal telopeptide (uNTx). The main outcome of interest was the correlation of disease activity with concentrations of bone turnover markers in Paget's disease patients before and after treatment with bisphosphonates. Correlation coefficients were pooled across studies using the random effects model.
RESULTS
We included 17 observational studies and one trial reporting on 953 patients. Prior to treatment, all studied bone turnover markers had moderate to strong correlation with scintigraphic indices (correlation coefficients ranging from 0.58 to 0.80) with no statistically significant difference between the bone turnover markers overall (p = 0.08). P1NP, uNTx, and bone ALP tend to have higher correlation with scintigraphy. After starting treatment with bisphosphonate, there was moderate to strong correlation with disease activity with all markers except bone ALP (correlation coefficients ranging from 0.43 to 0.70).
CONCLUSION
The findings of this meta-analysis suggest the Paget's disease activity is best monitored by following P1NP levels. However, total ALP, bone ALP, and uNTx are good alternatives as markers of disease activity in untreated patients. Total ALP and uNTx can be useful in following patients with Paget's disease after treatment if P1NP is not available. Clinicians, however, should take availability, cost, and the presence of liver disease into consideration when deciding which bone turnover marker is most appropriate when evaluating patients with Paget's disease.
Topics: Alkaline Phosphatase; Biomarkers; Bone Density Conservation Agents; Bone Remodeling; Diphosphonates; Humans; Osteitis Deformans; Radionuclide Imaging
PubMed: 26037791
DOI: 10.1007/s00198-015-3095-0 -
Bone Aug 2013Several studies have suggested that the prevalence and severity of PDB have fallen in recent years. The magnitude of this trend and its globalization have not been well... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Several studies have suggested that the prevalence and severity of PDB have fallen in recent years. The magnitude of this trend and its globalization have not been well established.
OBJECTIVE
The objective of this study is to estimate the pooled magnitude of the changes in the prevalence of PDB and as a secondary objective, to make up a world atlas of PDB prevalence.
METHODS
A systematic review of English and non-English articles using MEDLINE (1946 to 2013) and EMBASE (1980 to 2013) was the method used. Search terms included epidemiology, incidence, prevalence, cohort studies, osteitis deformans or Paget's disease of bone. Studies with incidence and/or prevalence rate for PDB were included. Two authors independently extracted the data using predefined data fields and quality assessment. A pooled analysis based on random-effects models was carried out for secular trends.
RESULTS
Twenty-eight articles documented the prevalence of PDB; four articles the incidence and two articles the rate of new referrals. The prevalence of PDB varied greatly between the different countries, from 0.00028% in Japan to 5.4% in the UK. There were available data on changes in prevalence from two different surveys over two different time frames in Europe and New Zealand. In all but one city (Turin), a drop in the prevalence of PDB was recorded (pooled OR 0.64; 95% CI 0.45-0.91).
CONCLUSION
The incidence and prevalence rates of PDB vary widely between populations but both have decreased in most regions over recent years. The changes are heterogeneous however and within countries, the largest changes have been in areas that previously had a high prevalence. The reasons for these changes remain unclear at present but are likely to be due to an interaction between genetic factors and environmental triggers which may differ in different regions.
Topics: Humans; Incidence; Osteitis Deformans; Prevalence
PubMed: 23643679
DOI: 10.1016/j.bone.2013.04.024 -
Clinical presentation of Paget's disease: evaluation of a contemporary cohort and systematic review.Calcified Tissue International Nov 2014Paget's disease of bone (PDB) has become less common over recent decades but it is unclear if this has impacted on clinical presentation. Here we evaluated the... (Review)
Review
Paget's disease of bone (PDB) has become less common over recent decades but it is unclear if this has impacted on clinical presentation. Here we evaluated the presenting features of PDB in a contemporary cohort of UK patients and conducted a systematic review of studies in which the presenting features had been reported. The case series comprised 88 patients referred to a specialist clinic between 2005 and 2013. Bone pain was the most common presenting feature occurring in 73.8% of patients. Others included bone deformity (18.1%), deafness (7.9%) and pathological fracture (5.7%). The disease was asymptomatic in 22% of cases. Antiresorptive treatment was given for pain in 34 cases and 61.7% of patients responded. Patients with a shorter disease duration were more likely to respond (p = 0.047). In the systematic review, bone pain was the most common presenting feature (52.2% of cases) followed by deformity (21.5%), deafness (8.9%) and fracture (8.5%). Time trend analysis in subjects of European descent showed that fracture was less common in studies performed during the past 25 years as compared with older studies (5.5 vs. 10.8% p < 0.001) whereas pain was more common (54.3 vs. 48.3%, p = 0.003). While changes in the mode of presentation of PDB have occurred over recent years, many patients present with complications such as fracture and deformity. Further research is required to determine if early detection and therapeutic intervention might be of value in preventing the morbidity associated with this common disease.
Topics: Aged; Cohort Studies; Female; Humans; Male; Middle Aged; Osteitis Deformans
PubMed: 25160936
DOI: 10.1007/s00223-014-9904-1 -
The Cochrane Database of Systematic... Dec 2017Bisphosphonates are considered to be the treatment of choice for people with Paget's disease of bone. However, the effects of bisphosphonates on patient-centred outcomes... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bisphosphonates are considered to be the treatment of choice for people with Paget's disease of bone. However, the effects of bisphosphonates on patient-centred outcomes have not been extensively studied. There are insufficient data to determine whether reducing and maintaining biochemical markers of bone turnover to within the normal range improves quality of life and reduces the risk of complications.
OBJECTIVES
To assess the benefits and harms of bisphosphonates for adult patients with Paget's disease of bone.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, ISI Web of Knowledge and trials registers up to March 2017. We searched regulatory agency published information for rare adverse events.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of bisphosphonates as treatment for Paget's disease in adults.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened search results, extracted data and assessed studies for risk of bias. We used standard methodological procedures expected by The Cochrane Collaboration.
MAIN RESULTS
We included 20 trials (25 reports, 3168 participants). Of these, 10 trials (801 participants) compared bisphosphonates (etidronate, tiludronate, ibandronate, pamidronate, olpadronate, alendronate, risedronate, zoledronate) versus placebo, seven compared two bisphosphonates (992 participants), one trial compared a bisphosphonates with a bisphosphonate plus calcitonin (44 participants), and two studies, the largest trial (1331 participants) and its interventional extension study (502 participants), compared symptomatic treatment and intensive treatment where the goal was to normalise alkaline phosphatase.Most studies were assessed at low or unclear risk of bias. Six of 10 studies comparing bisphosphonates versus placebo were assessed at high risk of bias, mainly around incomplete outcome data and selective outcome reporting.Participant populations were reasonably homogeneous in terms of age (mean age 66 to 74 years) and sex (51% to 74% male). Most studies included participants who had elevated alkaline phosphatase levels whether or not bone pain was present. Mean follow-up was six months.Bisphosphonates versus placeboBisphosphonates tripled the proportion (31% versus 9%) of participants whose bone pain disappeared (RR 3.42, 95% confidence interval (CI) 1.31 to 8.90; 2 studies, 205 participants; NNT 5, 95% CI 1 to 31; moderate-quality evidence). This result is clinically important. Data were consistent when pain change was measured as any reduction (RR 1.97, 95% CI 1.29 to 3.01; 7 studies, 481 participants).There was uncertainty about differences in incident fractures: 1.4% fractures occurred in the bisphosphonates group and none in the placebo group (RR 0.89, 95% CI 0.18 to 4.31; 4 studies, 356 participants; very low-quality evidence).None of the studies reported data on orthopaedic surgery, quality of life or hearing thresholds.Results regarding adverse effects and treatment discontinuation were uncertain. There was a 64% risk of mild gastrointestinal adverse events in intervention group participants and 48% in the control group (RR 1.32, 95% CI 0.91 to 1.92; 6 studies, 376 participants; low-quality evidence). The likelihood of study participants discontinuing due to adverse effects was slightly higher in intervention group participants (4.4%) than the control group (4.1%) (RR 1.01, 95% CI 0.41 to 2.52; 6 studies, 517 participants; low-quality evidence). Zoledronate was associated with an increased risk of transient fever or fatigue (RR 2.57, 95% CI 1.21 to 5.44; 1 study, 176 participants; moderate-quality evidence).Bisphosphonates versus active comparatorMore participants reported pain relief with zoledronate than pamidronate (RR 1.30, 95% CI 1.10 to 1.53; 1 study, 89 participants; NNT 5, 95% CI 3 to 11) or risedronate (RR 1.36, 95% CI 1.06 to 1.74; 1 study, 347 participants; NNT 7, 95% CI 4 to 24; very low quality evidence). This result is clinically important.There was insufficient evidence to confirm or exclude differences in adverse effects of bisphosphonates (RR 1.05, 95% CI 0.95 to 1.76; 2 studies, 437 participants; low-quality evidence) and treatment discontinuation (2 studies, 437 participants) (RR 2.04, 95% CI 0.43 to 9.59; 2 studies, 437 participants; very low-quality evidence).Intensive versus symptomatic treatmentThere was no consistent evidence of difference to response in bone pain, bodily pain or quality of life in participants who received intensive versus symptomatic treatment.Inconclusive results were observed regarding fractures and orthopaedic procedures for intensive versus symptomatic treatment (intensive treatment for fracture: RR 1.84, 95% CI 0.76 to 4.44; absolute risk 8.1% versus 5.2%; orthopaedic procedures: RR 1.58, 95% CI 0.80 to 3.11; absolute risk 5.6% versus 3.0%; 1 study, 502 participants; low-quality evidence).There was insufficient evidence to confirm or exclude an important difference in adverse effects between intensive and symptomatic treatment (RR 1.05, 95% CI 0.79 to 1.41; low-quality evidence).There was insufficient evidence to confirm or exclude an important difference of risk of rare adverse events (including osteonecrosis of the jaw) from the regulatory agencies databases.
AUTHORS' CONCLUSIONS
We found moderate-quality evidence that bisphosphonates improved pain in people with Paget's disease of bone when compared with placebo. We are uncertain about the results of head-to-head studies investigating bisphosphonates. We found insufficient evidence of benefit in terms of pain or quality of life from intensive treatment. Information about adverse effects was limited, but serious side effects were rare, and rate of withdrawals due to side effects was low.
Topics: Aged; Alkaline Phosphatase; Bone Density Conservation Agents; Calcitonin; Diphosphonates; Female; Humans; Male; Musculoskeletal Pain; Osteitis Deformans; Patient Dropouts; Randomized Controlled Trials as Topic
PubMed: 29192423
DOI: 10.1002/14651858.CD004956.pub3 -
European Journal of Orthopaedic Surgery... Jan 2016Paget's disease of bone (PDB) is a disease characterized by a disorder in the bone metabolism. The spine is the second region affected after the pelvis. Surgical... (Review)
Review
Paget's disease of bone (PDB) is a disease characterized by a disorder in the bone metabolism. The spine is the second region affected after the pelvis. Surgical treatment is reserved for cases refractory to medical treatment. We performed a systematic review of patients with Paget disease of bone affecting the spine, treated surgically in the last 30 years. The main objective of the review is to find out indications for surgery, outcomes of these patients and also the standard perioperative management.
Topics: Bone Cements; Bone Density Conservation Agents; Cervical Vertebrae; Diphosphonates; Humans; Lumbar Vertebrae; Osteitis Deformans; Polymethyl Methacrylate; Postoperative Complications; Preoperative Care; Spinal Diseases; Thoracic Vertebrae; Treatment Outcome
PubMed: 26126588
DOI: 10.1007/s00590-015-1659-5 -
The American Journal of Medicine Jun 2008Bisphosphonates are medications that impact bone reformation by inhibiting osteoclast function. Osteonecrosis of the jaw has been reported among patients receiving these... (Review)
Review
BACKGROUND
Bisphosphonates are medications that impact bone reformation by inhibiting osteoclast function. Osteonecrosis of the jaw has been reported among patients receiving these medications. It is unclear if the risk factors associated with osteonecrosis of the jaw among cancer patients taking bisphosphonates also are possible risk factors among patients receiving these medications for other indications.
METHODS
A systematic review search strategy was used to identify cases of osteonecrosis of the jaw among patients taking bisphosphonates for an indication other than cancer to identify potential contributing factors. Data were analyzed according to previous models to develop a more expanded model that may explain possible mechanisms for the development of osteonecrosis of the jaw among patients without cancer.
RESULTS
Ninety-nine cases of osteonecrosis of the jaw were identified among patients who were prescribed a bisphosphonate for an indication other than cancer. These cases included 85 osteoporosis patients, 10 patients with Paget's disease, 2 patients with rheumatoid arthritis, 1 patient with diabetes, and 1 patient with maxillary fibrous dysplasia. The mean age was 69.4 years, 87.3% were female, and 83.3% were receiving oral, but not intravenous, bisphosphonates. Of the 63 patients reporting dental care information, 88.9% had a dental procedure before the onset of osteonecrosis of the jaw. Of all cases providing medical information, 71% were taking at least one medication that affects bone turnover in addition to the bisphosphonate, and 81.3% reported additional underlying health conditions.
CONCLUSIONS
The case details suggest a multiplicity of factors associated with this condition and provide the foundation for a model outlining the potential mechanism for the development of osteonecrosis of the jaw among patients taking bisphosphonates for an indication other than cancer.
Topics: Comorbidity; Dental Prophylaxis; Diphosphonates; Humans; Jaw Diseases; Neoplasms; Oral Surgical Procedures; Osteitis Deformans; Osteonecrosis; Osteoporosis; Risk Factors; Tooth Diseases
PubMed: 18501224
DOI: 10.1016/j.amjmed.2008.01.047 -
The Journal of Arthroplasty Jul 2023Patients who have Paget's Disease more frequently require total hip arthroplasty (THA) and total knee arthroplasty (TKA) than matched controls. However, controversy...
BACKGROUND
Patients who have Paget's Disease more frequently require total hip arthroplasty (THA) and total knee arthroplasty (TKA) than matched controls. However, controversy remains regarding their outcome. We aimed to evaluate the literature regarding outcomes following THA and TKA in patients who have Paget's Disease.
METHODS
MEDLINE, EMBASE and Cochrane databases were searched for all articles evaluating outcomes following THA and TKA in patients who have Paget's Disease. Quality of included studies was assessed using the Newcastle-Ottawa Scale.
RESULTS
A total of 19 articles (published between 1976 and 2022) were included, comprising 58,695 patients (48,766 controls and 10,018 patients who have Pagets Disease), from 209 potentially relevant titles. Patients with Paget's Disease have a pooled mortality of 32.5% at a mean of 7.8 years (range, 0.1 to 20) following THA and 31.0% at a mean of 8.5 years (range, 2 to 20) following TKA, with a pooled revision rate of 4.4% at 7.2 years (range, 0 to 20) following THA and 2.2% at 7.4 years (range, 2 to 20) following TKA. Renal and respiratory complications, as well as heterotopic ossification and surgical-site infection were the most common post-operative complications.
CONCLUSION
There is marked heterogeneity in outcome reporting of studies assessing arthroplasty in patients who have Paget's Disease, with studies of low to moderate quality. Patients with Paget's Disease undergoing THA and TKA appear to have similar implant longevity as their unaffected counterparts. However, they appear to have an increased risk of medical and surgical complications and may have a higher mortality risk from their procedure.
Topics: Humans; Arthroplasty, Replacement, Knee; Osteitis Deformans; Arthroplasty, Replacement, Hip; Surgical Wound Infection; Postoperative Complications
PubMed: 36639114
DOI: 10.1016/j.arth.2023.01.004 -
Reviews in Endocrine & Metabolic... Dec 2020Paget's disease of bone (PDB) is a metabolic bone disease with distinct geographical and ethnic differences in its pathogenesis. In this study, we aimed to...
Paget's disease of bone (PDB) is a metabolic bone disease with distinct geographical and ethnic differences in its pathogenesis. In this study, we aimed to retrospectively analyze the clinical features and the status of diagnosis and treatment of PDB in mainland China to improve the clinician's understanding of this disease. For this purpose, we conducted a systematic review of 118 articles, including a total of 332 patients with PDB. The results showed that the onset age of PDB in mainland China was 46-60 years. The number of male patients in most age groups was slightly higher than that of female patients, but there was no statistical difference (p > 0.05). The gender ratio (male to female) of PDB in mainland China was significantly different from that in Japan (p < 0.05), but not from that in the USA (p > 0.05). The clinical manifestations of PDB patients in mainland China mainly included ostealgia, bone malformation, hearing loss, and fracture, and bisphosphonate was used as the main treatment drug. These findings were similar to those in Japan, UK, and USA. Total alkaline phosphatase (TALP) level was elevated in about 89.7% of patients, and no correlation between TALP level and ostealgia was observed (p > 0.05). In addition, no difference in TALP level between males and females in each group was observed (p > 0.05).
Topics: Adult; Aged; Aged, 80 and over; China; Female; Humans; Male; Middle Aged; Osteitis Deformans
PubMed: 32115673
DOI: 10.1007/s11154-020-09544-x -
Clinical Rheumatology Apr 2018The objective of this study is to report a Brazilian patient and his family with inclusion body myopathy associated with Paget's disease of bone and frontotemporal... (Review)
Review
The objective of this study is to report a Brazilian patient and his family with inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD). A systematic review of the literature on the valosin-containing protein (VCP) mutation was also performed. The proband (patient) was initially treated as a case of possible refractory polymyositis with Paget's disease and later as an inclusion body myopathy. However, after admission to our service, and considering his personal and familial antecedents, whole exome sequencing was performed revealing valosin-containing protein (VCP) c.290G>A (p.Gly97Glu) mutation in the patient and his nine family members. The clinical presentation of the patient and his family was characterized by different degrees and evaluations of IBMPFD. According to the literature, only one family (Chinese) has this same VCP mutation concomitantly with different IBMPFD phenotype manifestations. The present study shows that IBMPFD should be considered as a differential diagnosis in patients with inflammatory myopathies associated to bone disease and/or cognitive impairment. Moreover, the study expands the genotypic spectrum of missense mutations of VCP gene in a Brazilian family with variable phenotypes.
Topics: Brazil; Female; Frontotemporal Dementia; Genotype; Humans; Male; Middle Aged; Muscular Dystrophies, Limb-Girdle; Myositis, Inclusion Body; Osteitis Deformans; Pedigree; Phenotype; Valosin Containing Protein
PubMed: 29127544
DOI: 10.1007/s10067-017-3913-1 -
World Neurosurgery Mar 2020Paget's disease of the bone (PDB) is a focal bone disorder characterized by excessive resorption and deposition of pathologic bone. It can involve the skull and cause...
OBJECTIVE
Paget's disease of the bone (PDB) is a focal bone disorder characterized by excessive resorption and deposition of pathologic bone. It can involve the skull and cause neurologic dysfunction. Hydrocephalus occurring as a complication has also been reported. However, owing to its rarity, the optimal treatment has not yet been determined.
METHODS
We report the case of a 60-year-old woman with a diagnosis of PDB who had presented with symptomatic hydrocephalus and was successfully treated with ventriculoperitoneal shunt insertion. We also performed a systematic review of the Scopus and PubMed databases for case reports and series documenting patients with PDB complicated by hydrocephalus and discussed the clinical features and therapeutic strategies used.
RESULTS
We found 28 cases of PDB complicated by hydrocephalus in reported studies, including the present case. The median age was 67 years (range, 48-85 years; interquartile range, 7 years), with a female sex predilection. The most common neurologic manifestations were cognitive impairment, gait unsteadiness, urinary incontinence, hearing loss, and headache. Surgery had been performed in 73% of the 28 cases. The most common operation was insertion of a ventriculoperitoneal shunt (63.2%). Cerebrospinal fluid diversion resulted in significant or complete neurologic recovery in 78.9% of the 28 patients. Posterior fossa decompression was performed in 15.8% of operative cases but did not significantly alter the clinical course.
CONCLUSION
Patients with hydrocephalus occurring as a complication of PDB will most commonly present with cognitive impairment, gait unsteadiness, and urinary incontinence. Surgery plays an important role in the treatment, with CSF diversion procedures resulting in significant neurologic recovery in most cases.
Topics: Aged; Aged, 80 and over; Female; Humans; Hydrocephalus; Male; Middle Aged; Osteitis Deformans; Ventriculoperitoneal Shunt
PubMed: 31881339
DOI: 10.1016/j.wneu.2019.12.099