A case series of Paget's disease of bone in Chinese

Wat, Winnie Zee Man; Cheung, William Sk; Lau, Tina W S

doi:10.12809/hkmj133661

Cited by 7 publications

(9 citation statements)

References 25 publications

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“…To the best of our knowledge, no more than 200 patients have been reported prior to the study in the literature in English and or in the local language. 23, 24 Hence, because they are common, SNPs were not considered likely to be causal, and mutations in unknown genes were further investigated.…”

Section: Discussionmentioning

confidence: 99%

A FKBP5 mutation is associated with Paget’s disease of bone and enhances osteoclastogenesis

Jiao

Yinchang

et al. 2017

Exp Mol Med

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Paget's disease of bone (PDB) is a common metabolic bone disease that is characterized by aberrant focal bone remodeling, which is caused by excessive osteoclastic bone resorption followed by disorganized osteoblastic bone formation. Genetic factors are a critical determinant of PDB pathogenesis, and several susceptibility genes and loci have been reported, including SQSTM1, TNFSF11A, TNFRSF11B, VCP, OPTN, CSF1 and DCSTAMP. Herein, we report a case of Chinese familial PDB without mutations in known genes and identify a novel c.163G>C (p.Val55Leu) mutation in FKBP5 (encodes FK506-binding protein 51, FKBP51) associated with PDB using whole-exome sequencing. Mutant FKBP51 enhanced the Akt phosphorylation and kinase activity in cells. A study of osteoclast function using FKBP51V55L KI transgenic mice proved that osteoclast precursors from FKBP51V55L mice were hyperresponsive to RANKL, and osteoclasts derived from FKBP51V55L mice displayed more intensive bone resorbing activity than did FKBP51WT controls. The osteoclast-specific molecules tartrate-resistant acid phosphatase, osteoclast-associated receptor and transcription factor NFATC1 were increased in bone marrow-derived monocyte/macrophage cells (BMMs) from FKBP51V55L mice during osteoclast differentiation. However, c-fos expression showed no significant difference in the wild-type and mutant groups. Akt phosphorylation in FKBP51V55L BMMs was elevated in response to RANKL. In contrast, IκB degradation, ERK phosphorylation and LC3II expression showed no difference in wild-type and mutant BMMs. Micro-CT analysis revealed an intensive trabecular bone resorption pattern in FKBP51V55L mice, and suspicious osteolytic bone lesions were noted in three-dimensional reconstruction of distal femurs from mutant mice. These results demonstrate that the mutant FKBP51V55L promotes osteoclastogenesis and function, which could subsequently participate in PDB development.

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Section: Discussionmentioning

confidence: 99%

A FKBP5 mutation is associated with Paget’s disease of bone and enhances osteoclastogenesis

Jiao

Yinchang

et al. 2017

Exp Mol Med

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“…This frequency is much lower in the Scandinavian countries, Eastern Europe and Asia [2,3]. Finally, Paget's disease remains exceptional in Africa, particularly in sub-Saharan areas in particular in patients with black skin [4][5][6]. This observation is one of very few cases described in sub-Saharan Africa.…”

Section: Discussionmentioning

confidence: 97%

Maladie de Paget au Sénégal : à propos de deux cas dans une population noire africaine

Diédhiou¹,

Fall²,

Soko³

et al. 2016

Batna J Med Sci

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Mr. MD is a 72-years-old man, admitted for spontaneous, permanent, crushing type pain on the pelvis above the right hip evolving for two years, without night or morning stiffness but increasing with hearing loss, temporal and parietal headache. Physical examination showed a painful hip in active and passive mobilization. Pressure on iliac spines and lower lumbar and sacrococcygeal bones was painful. The patient showed no inflammatory syndrome. Serum calcium was normal. We noted an isolated increase in alkaline phosphatase levels to 401 IU/l. Radiographs showed bilateral heterogeneous sclerosis of the iliac bone with thickening lines and and almost disappearance of the right hip joint space. There was a marked thickening of the cortex on the femoral proximal third and thickening of the cranial vault. MRI showed cortical thickening of the right pelvic bone, a T1 hyper signal, and an intermediate T2 signal with fat/sat. This was pathognomonic of Paget's disease. The second patient is a 72-year-old man with no history, having intense pain on the right side of the lower limb. Physical examination showed no musculoskeletal deformity, but pain on palpation and mobilization of the right hip. Serum alkaline phosphatase (ALP) was raised to 4 times the normal range. Radiography showed cortical thickening of the ischial pubic branch, a heterogeneous sclerosis gypsy moth of the iliac wing, a steady narrowing of the femoral hip-spaced lines and thickening of the iliac ischial pubic. This aspect is pathognomonic of Paget’s disease, the patient underwent treatment with zoledronic acid intravenously at 5 mg. The outcome was favorable up to 10 months with reduced pain (VAS = 2/10) and normal PAL.

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“…For unknown reason, there is great discrepancy in the prevalence and incidence of the disease among different ethnic groups. The disease is common in the UK, Australia, North American, and Western Europe but is very rare in North Europe, Asia, and Africa 20–22. Some epidemiological data also revealed a fall in prevalence and clinical severity of the disease in developed countries, which is postulated due to changes in ethnic constitution of the population or in environmental triggers 23,24…”

Section: Paget’s Disease Of Bonementioning

confidence: 99%

Current perspectives on bisphosphonate treatment in Paget’s disease of bone

Wat¹

2014

TCRM

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Paget’s disease of bone is a chronic metabolic bone disease with focal increase in bone turnover. The exact etiology of the disease is uncertain, although genetic and environmental factors are believed to be important. Bisphosphonate is the main class of medication being used to control disease activity via its antiresorptive effect. This review discusses the controversies concerning the use of bisphosphonates in the treatment of Paget’s disease of bone, the efficacy of different bisphosphonates in controlling disease activity, and the possible rare side effects of bisphosphonates. Symptoms are the main indication for treatment in Paget’s disease of bone. As treatment benefits in asymptomatic individuals remain controversial and nonevidence based, the decision to treat these patients should be individualized to their risk and benefit profiles. There are several trials conducted to evaluate and compare the efficacy of different regimes of bisphosphonates for treating Paget’s disease of bone. Most trials used biochemical markers rather than clinical symptoms or outcomes as parameters for comparison. Zoledronate is an attractive option as it can achieve high rates of biochemical remission and sustain long duration of suppression by a single dose. Atypical femoral fracture and osteonecrosis of the jaw are two rare and severe side effects reported, possibly related to the use of bisphosphonates in patients with osteoporosis and malignancy-induced hypercalcemia. As the regimes of bisphosphonates used for treating Paget’s disease of bone are different from those two diseases, the risks of developing these two possible side effects are expected to be very low, although this remains unknown. Vitamin D and calcium supplement should be given to patients at risk of vitamin D insufficiency when given zoledronate, as symptomatic hypocalcemia may develop. For those intolerant of bisphosphonates, subcutaneous calcitonin can be used for a limited period due to its associated risk of malignancy.

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A case series of Paget's disease of bone in Chinese

Cited by 7 publications

References 25 publications

A FKBP5 mutation is associated with Paget’s disease of bone and enhances osteoclastogenesis

A FKBP5 mutation is associated with Paget’s disease of bone and enhances osteoclastogenesis

Maladie de Paget au Sénégal : à propos de deux cas dans une population noire africaine

Current perspectives on bisphosphonate treatment in Paget’s disease of bone

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A case series of Paget's disease of bone in Chinese

Cited by 7 publications

References 25 publications

A FKBP5 mutation is associated with Paget’s disease of bone and enhances osteoclastogenesis

A FKBP5 mutation is associated with Paget’s disease of bone and enhances osteoclastogenesis

Maladie de Paget au Sénégal : à propos de deux cas dans une population noire africaine

Current perspectives on bisphosphonate treatment in Paget&rsquo;s disease of bone

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Current perspectives on bisphosphonate treatment in Paget’s disease of bone