Active Paget's Disease Of Bone Research Articles

Tartrate-resistant acid phosphatase 5b, but not periostin, is useful for assessing Paget's disease of bone.

Periostin is a matricellular protein with a preferential location in cortical bone and periosteal tissue, and tartrate-resistant acid phosphatase 5b (TRAP5b) is a marker of osteoclast numbers. In Paget's disease of bone (PDB), there is increased cortical thickening and probably increased periosteal apposition, along with increased osteoclast numbers. To analyse if circulating periostin is a biomarker for PDB, and if it is associated with disease activity and involvement of long bones that represent major cortical contribution. Also, to analyse whether TRAP5b, a scarcely explored bone resorption marker, is useful in the assessment of PDB. We recruited 42 patients with PDB (13F/29M; 71 ± 11.6 yrs). 71.4% had active disease, 66.6% had polyostotic disease and 54.8% had long bone involvement. Blood and urine samples were taken between 8:00 and 10:00 A.M. after an overnight fast. Periostin and TRAP5b were measured in serum, using commercial ELISA assays (Biomedica and IDS, respectively). Serum total ALP, PINP, CTX, bone ALP and urinary NTX were measured. Reference values for periostin and TRAP5b were obtained from 45 healthy subjects. Serum periostin did not differ between patients and controls (989.4 ± 173.2 vs. 966.9 ± 195.4 pMol/L, p = 0.572). No significant differences were observed between patients with and without active disease (964.5 ± 168.8 vs.1051.6 ± 175.6 pMol/L, p = 0.143), involvement or not of long bones (1022.2 ± 145.8 vs 949.7 ± 198.2 pMol/L, p = 0.181) and monostotic or polyostotic disease (963.8 ± 198.7 vs 1002.2 ± 161.4 pMol/L, p = 0.505). There were significant correlations between serum periostin and all bone turnover markers (bone ALP, PINP, uNTX, sCTX and TRAP5b) in PDB patients with active disease, but not in the inactive PDB group. Serum TRAP5b was significantly higher in PDB patients than in controls (4.43 ± 1.76 vs. 3.21 ± 1.02 U/L, p < 0.001), in those with active disease (4.98 ± 1.76 vs. 3.07 ± 0.72 U/L, p < 0.001) and in patients with polyostotic disease than in those with monostotic disease (4.81 ± 1.79 vs 3.68 ± 1.5 U/L, p = 0.005). TRAP5b levels were not influenced by previous bisphosphonate treatment (4.14 ± 1.42 vs. 4.84 ± 2.02 U/L, p = 0.206). Periostin is not useful for assessing PDB, whilst TRAP5b, which has been a scarcely explored bone turnover marker until now, may be useful in the analysis of this disease, providing new information on the resorption process. In addition, periostin levels correlate with all classical BTMs in active PDB, suggesting that this marker may reflect periosteal and cortical metabolism in accelerated bone turnover states.

Diagnosis and Management of Paget's Disease of Bone in Adults: A Clinical Guideline.

ABSTRACTAn evidence‐based clinical guideline for the diagnosis and management of Paget's disease of bone (PDB) was developed using GRADE methodology, by a Guideline Development Group (GDG) led by the Paget's Association (UK). A systematic review of diagnostic tests and pharmacological and nonpharmacological treatment options was conducted that sought to address several key questions of clinical relevance. Twelve recommendations and five conditional recommendations were made, but there was insufficient evidence to address eight of the questions posed. The following recommendations were identified as the most important: 1) Radionuclide bone scans, in addition to targeted radiographs, are recommended as a means of fully and accurately defining the extent of metabolically active disease in patients with PDB. 2) Serum total alkaline phosphatase (ALP) is recommended as a first‐line biochemical screening test in combination with liver function tests in screening for the presence of metabolically active PDB. 3) Bisphosphonates are recommended for the treatment of bone pain associated with PDB. Zoledronic acid is recommended as the bisphosphonate most likely to give a favorable pain response. 4) Treatment aimed at improving symptoms is recommended over a treat‐to‐target strategy aimed at normalizing total ALP in PDB. 5) Total hip or knee replacements are recommended for patients with PDB who develop osteoarthritis in whom medical treatment is inadequate. There is insufficient information to recommend one type of surgical approach over another. The guideline was endorsed by the European Calcified Tissues Society, the International Osteoporosis Foundation, the American Society of Bone and Mineral Research, the Bone Research Society (UK), and the British Geriatric Society. The GDG noted that there had been a lack of research on patient‐focused clinical outcomes in PDB and identified several areas where further research was needed. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

Response to Zoledronic Acid in Patients with Active Paget's Disease of Bone: A Retrospective Study.

Background:Traditionally, bisphosphonates are used to treat active Paget's disease of bone (PDB). Intravenous zoledronic acid (ZA) is the most effective treatment option leading to sustained remission.Objective:The primary objective of this study was to analyze the effect of intravenous ZA in patients with active PDB in a tertiary care center of India.Materials and Methods:Retrospective data of 13 patients with active PDB who received a single dose of 4 mg intravenous ZA at our institute from January 2011 to June 2017 were reviewed. Response to therapy was monitored clinically, biochemically by serum alkaline phosphatase (ALP), and scintigraphically by 99m-Technetium methylene diphosphonate bone scan.Results:All of our patients reported relief of bone pain. The mean duration of follow-up in our study was 35.2 ± 16.8 months. Serum ALP levels reduced significantly from 1190.9 ± 666.1 IU/L (n = 13) at baseline to 200.5 ± 68.4 IU/L (n = 13) at 6 months (P < 0.001). ALP level at 1 year was 174 ± 33.6 IU/L (n = 12), which remained stable till 36 months at 176.5 ± 50 IU/L (n = 8). This indicates that remission achieved by 6 months post ZA is sustained for at least 3 years. Scintigraphic ratio reduced from 9.6 [interquartile range (IQR) 5.25–18.2] at baseline to 2.7 (IQR 1.20–4.05) at follow-up (P < 0.001). Similarly, scintigraphic index of involvement reduced from 9.9 (IQR 5.6–28.5) at baseline to 3 (IQR 2–4) at follow-up (P = 0.018).Conclusion:A 4 mg single dose of intravenous ZA results in clinical, biochemical, and scintigraphic response that is sustained for at least 3 years.

AB1049 Characterization and incidence on acute phase reaction in paget’s disease after zoledronic acid infusion

BackgroundZoledronic acid (AZ), characterized by its high antiresorptive activity, has restored the excessive pagetic bone remodeling, reduce or suppress the biological activity, influence on clinical features, and prevent the onset...

Comparison of intravenous and intramuscular neridronate regimens for the treatment of paget disease of bone

Aminobisphosphonates actually represent the most common treatment for Paget disease of bone (PDB). In a previous study we demonstrated that either zoledronic acid (4 mg) or neridronate (200 mg) given as a single intravenous infusion showed a similar short-term efficacy in achieving biochemical remission in up to 90% of patient nonresponders to pamidronate. In this study we compared the long-term (36 months) effects of a same neridronate dose (200 mg) given as an intravenous (100-mg infusion for 2 consecutive days) or intramuscular (25-mg injection weekly for 2 months) regimen in 56 patients with active PDB. All patients were advised to receive calcium plus vitamin D supplementation throughout the study period. At 6 months, 92.6% and 96.5% of patients receiving intravenous and intramuscular neridronate, respectively, achieved a therapeutic response [defined as normalization of alkaline phosphatase (ALP) levels or a reduction of at least 75% in total ALP excess]. The response to treatment was significantly correlated with baseline ALP and 25-hydroxyvitamin D [25(OH)D] levels at 6 months. The decrease in ALP levels was highest in patients with higher baseline total or bone-specific ALP levels and with higher 25(OH)D levels at 6 months. Response rates were maintained at 12 months but decreased progressively at 24 and 36 months without significant differences between the two neridronate regimens. Both regimens were well tolerated. The only relevant side effect was an acute-phase response occurring in 14% of the patients. In conclusion, these results indicate that a 200-mg intramuscular neridronate course has a similar efficacy as an intravenous infusion of the same dose for the treatment of PDB and might be of particular value for patients intolerant to oral bisphosphonates and unwilling or unable to undergo intravenous infusions.

Pamidronate and Zoledronic Acid in the Treatment of Paget's Disease of Bone

Paget's disease of bone (PDB) is a condition characterized by excessive and abnormal bone remodelling. Due to a high rate of bone remodelling, bisphosphonates, and especially pamidronate and the newer zolendronate, are indicated in the treatment of PDB. The presence of asymptomatic, but active PDB represents an indication for treatment aimed at preventing later complications. An additional indication for treatment is the involvement of skeletal segments that may give rise to severe complications. Pamidronate has a long history in the treatment of PDB. The more utilised regimen is 3 to 6 i.v. infusion of 60 mg of pamidronate at an infusion rate of 1 mg/min within 3-21 days. Zolendronate (5 mg once yearly) is the most powerful amino-bisphosphonate currently used. This primacy recognizes both the ability to inhibit the farnesyl-pyrophosphate synthetase and the higher affinity to hydroxyapatite crystals as a cause. Both pamidronate and zolendronate are effective in PDB, with an evidence-based superiority of the latter.

Comparison of Different Intravenous Bisphosphonate Regimens for Paget's Disease of Bone

This randomized study compared different intravenous bisphosphonates in PDB. Zoledronate was superior with respect to pamidronate in achieving biochemical remission, with therapeutic response maintained in most patients at 15 mo. Single neridronate and zoledronate infusion showed a similar efficacy in up to 90% of patients nonresponders to pamidronate. Intravenous bisphosphonates represent a common therapy for Paget's disease of bone (PDB). However, there have been few head to head randomized trials comparing intravenous bisphosphonates. We performed a 15-mo, randomized study comparing different intravenous bisphosphonates in 90 subjects with active PDB. At baseline, patients were randomly assigned to receive pamidronate (30 mg, i.v., for 2 consecutive days every 3 mo; n = 60) or zoledronate (4 mg, i.v.; n = 30). After 6 mo, nonresponders to pamidronate were crossed over to zoledronate or neridronate (100 mg, i.v., for 2 consecutive days). The primary efficacy endpoint was therapeutic response at 6 mo, defined as normalization of alkaline phosphatase (ALP) or a reduction of at least 75% in total ALP excess. At 6 mo, 97% of patients receiving zoledronate had a therapeutic response compared with 45% of patients receiving pamidronate. Normalization of ALP was achieved in 93% of patients in the zoledronate group and in 35% of patients in the pamidronate group. ALP normalization was maintained in 79% and 65% of zoledronate-treated patients after 12 and 15 mo, respectively; loss of therapeutic response was observed in 2 of 30 (6%) at 12 and 15 mo. At 6 mo, 27 patients showing therapeutic response to pamidronate continued the treatment, whereas nonresponders were crossed-over to neridronate (n = 15) or zoledronate (n = 18). Among these subjects, 14 of 15 (93%) in the neridronate group and 17 of 18 (94%) in the zoledronate group achieved a therapeutic response. Similar normalization rates were observed between neridronate- (80%) and zoledronate- (83%) treated subjects. Normalization and therapeutic response were maintained at 9 mo from treatment (corresponding to 15 mo from the baseline visit) in either neridronate or zoledronate groups. Single neridronate and zoledronate infusion showed a similar efficacy in achieving biochemical remission in up to 90% of patients nonresponders to pamidronate. Therapeutic response to zoledronate seems to be maintained in most patients at 15 mo.

Discrepant blood concentrations of type I procollagen propeptides in active Paget disease of bone

Discrepant blood concentrations of type I procollagen propeptides in active Paget disease of bone