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Orphanet Journal of Rare Diseases Feb 2009Osteopetrosis ("marble bone disease") is a descriptive term that refers to a group of rare, heritable disorders of the skeleton characterized by increased bone density... (Review)
Review
Osteopetrosis ("marble bone disease") is a descriptive term that refers to a group of rare, heritable disorders of the skeleton characterized by increased bone density on radiographs. The overall incidence of these conditions is difficult to estimate but autosomal recessive osteopetrosis (ARO) has an incidence of 1 in 250,000 births, and autosomal dominant osteopetrosis (ADO) has an incidence of 1 in 20,000 births. Osteopetrotic conditions vary greatly in their presentation and severity, ranging from neonatal onset with life-threatening complications such as bone marrow failure (e.g. classic or "malignant" ARO), to the incidental finding of osteopetrosis on radiographs (e.g. osteopoikilosis). Classic ARO is characterised by fractures, short stature, compressive neuropathies, hypocalcaemia with attendant tetanic seizures, and life-threatening pancytopaenia. The presence of primary neurodegeneration, mental retardation, skin and immune system involvement, or renal tubular acidosis may point to rarer osteopetrosis variants, whereas onset of primarily skeletal manifestations such as fractures and osteomyelitis in late childhood or adolescence is typical of ADO. Osteopetrosis is caused by failure of osteoclast development or function and mutations in at least 10 genes have been identified as causative in humans, accounting for 70% of all cases. These conditions can be inherited as autosomal recessive, dominant or X-linked traits with the most severe forms being autosomal recessive. Diagnosis is largely based on clinical and radiographic evaluation, confirmed by gene testing where applicable, and paves the way to understanding natural history, specific treatment where available, counselling regarding recurrence risks, and prenatal diagnosis in severe forms. Treatment of osteopetrotic conditions is largely symptomatic, although haematopoietic stem cell transplantation is employed for the most severe forms associated with bone marrow failure and currently offers the best chance of longer-term survival in this group. The severe infantile forms of osteopetrosis are associated with diminished life expectancy, with most untreated children dying in the first decade as a complication of bone marrow suppression. Life expectancy in the adult onset forms is normal. It is anticipated that further understanding of the molecular pathogenesis of these conditions will reveal new targets for pharmacotherapy.
Topics: Adult; Bone Marrow Diseases; Child, Preschool; Fractures, Spontaneous; Genes, Dominant; Genes, Recessive; Humans; Infant, Newborn; Osteoclasts; Osteopetrosis; Prevalence
PubMed: 19232111
DOI: 10.1186/1750-1172-4-5 -
Saudi Medical Journal Jan 2015
Topics: Adult; Bone Neoplasms; Diagnosis, Differential; Female; Femoral Fractures; Fractures, Spontaneous; Humans; Osteitis Deformans
PubMed: 25630017
DOI: 10.15537/smj.2015.1.11249 -
The Journal of Nutrition, Health & Aging 2019Spontaneous insufficiency fractures are caused by normal or physiological stress on weakened bone. The leading cause of insufficiency fractures is osteoporosis which has...
Spontaneous insufficiency fractures are caused by normal or physiological stress on weakened bone. The leading cause of insufficiency fractures is osteoporosis which has a propensity to affect older patients. Other causes or associated factors are disorders which affect bone metabolism, collagen formation, bone remodelling and medications such as bisphosphonates and glucocorticoids. Pathological fractures and abuse are important causes of unexplained fractures which warrant careful consideration. Spontaneous fractures of the long bones affect on average 1% of nursing home residents per year and tend to occur in patients who are bed-bound with joint contractures. Preventative measures for spontaneous insufficiency fractures include optimising nutrition to include an adequate intake of protein, calcium and vitamin D, maintaining mobility and preventing long periods of bed-rest and treatment of underlying pre-disposing conditions.
Topics: Aged; Female; Fractures, Spontaneous; Humans; Male
PubMed: 31560035
DOI: 10.1007/s12603-019-1234-6 -
Orthopaedics & Traumatology, Surgery &... Feb 2016A fracture is defined as pathological when it arises in a bone tissue that has been modified and reshaped by a local or systemic pathological process. In children,... (Review)
Review
A fracture is defined as pathological when it arises in a bone tissue that has been modified and reshaped by a local or systemic pathological process. In children, pathological fractures can be secondary to several conditions, ranging from metabolic diseases to tumors, infections or neuromuscular pathologies. History, clinical examination and radiologic assessment are essential to making a diagnosis, to identifying the underlying cause and to planning the right treatment of a pathological fracture. Treatment must be tailored to both the fracture and the underlying cause. The objective of this work is to present the diagnostic approach and the course to follow when a child presents with a pathological fracture. The most common causes of pathological fractures, as well as their characteristics, will be described. Pathological fractures occurring in osteogenesis imperfecta and in abused children as well as stress fractures will not be discussed.
Topics: Adolescent; Bone Cysts; Bone Neoplasms; Child; Child, Preschool; Fractures, Spontaneous; Humans; Infant; Infant, Newborn; Osteomyelitis; Pseudarthrosis
PubMed: 26774903
DOI: 10.1016/j.otsr.2015.05.010 -
Orthopaedics & Traumatology, Surgery &... Feb 2017The diagnosis of pathological fracture should be considered routinely in patients with long limb-bone fractures. Investigations must be performed to establish the... (Review)
Review
The diagnosis of pathological fracture should be considered routinely in patients with long limb-bone fractures. Investigations must be performed to establish the diagnosis of pathological fracture then to determine that the bone lesion is a metastasis. In over 85% of cases, the clinical evaluation combined with a detailed analysis of the radiographs is sufficient to determine that the fracture occurred at a tumour site. Aetiological investigations establish that the tumour is a metastasis. In some patients, the diagnosis of metastatic cancer antedates the fracture. When this is not the case, a diagnostic strategy should be devised, with first- to third-line investigations. When these fail to provide the definitive diagnosis, a surgical biopsy should be performed. The primaries most often responsible for metastatic bone disease are those of the breast, lung, kidney, prostate, and thyroid gland. However, the survival gains provided by newly introduced treatments translate into an increased frequency of bone metastases from other cancers. The optimal treatment of a pathological fracture is preventive. The Mirels score is helpful for determining whether preventive measures are indicated. When selecting a treatment for a pathological fracture, important considerations are the type of tumour, availability of effective adjuvant treatments, and general health of the patient. Metastatic fractures are best managed by a multidisciplinary team. The emergent treatment should start with optimisation of the patient's general condition, in particular by identifying and treating metabolic disorders (e.g., hypercalcaemia) and haematological disorders. Treatment decisions also depend on the above-listed general factors, location of the tumour, and size of the bony defect. Prosthetic reconstruction is preferred for epiphyseal fractures and internal fixation for diaphyseal fractures.
Topics: Bone Neoplasms; Decision Support Techniques; Femoral Fractures; Fracture Fixation, Internal; Fractures, Bone; Fractures, Spontaneous; Humans
PubMed: 28089230
DOI: 10.1016/j.otsr.2016.11.001 -
The British Journal of Radiology Sep 2021To determine the incidence and causes of pathological fractures in paediatric bone tumours and tumour-like lesions, and to determine if they are predictive of benign...
OBJECTIVE
To determine the incidence and causes of pathological fractures in paediatric bone tumours and tumour-like lesions, and to determine if they are predictive of benign lesions.
METHODS AND MATERIALS
Retrospective review of children with suspected bone tumours referred to a specialist musculoskeletal oncology service between September 2019 and August 2020. Data recorded included patient age and gender, lesion location, the presence of a pathological fracture on the initial plain radiograph, and the final diagnosis made either by image-guided biopsy/curettage or based on typical imaging features.
RESULTS
231 patients were included with 233 lesions (138 males and 93 females with mean age 10.5 years, range 3 months-18 years). Final diagnosis was based on histology in 85 (36.5%) cases and imaging in 148 (63.5%) cases, 52 (22.3%) lesions classed as non-neoplastic, 139 (59.7%) as benign and 42 (18%) as malignant. Pathological fractures were seen in 41 cases (17.6%) at presentation, involving the humerus in 19 (46.3%), the femur in 14 (34.1%), the tibia in 3 (7.3%), the fibula and radius in two each (4.9%) and the second toe proximal phalanx in 1 (2.4%) ( < 0.001). The commonest underlying lesions included simple bone cyst ( = 17; 41.5%) and non-ossifying fibroma ( = 10; 24.4%). Only 4 cases (9.75%) were malignant, one case each of osteosarcoma, Ewing sarcoma, leukaemia and BCOR undifferentiated round cell sarcoma. Pathological fracture occurred in 27.7% of non-malignant lesions and 9.5% of malignant lesions, this difference being statistically significant ( < 0.001).
CONCLUSION
Pathological fractures were seen in 17.6% of paediatric bone tumours, tumour-like lesions, being significantly associated with humeral location and non-malignant diagnosis.
ADVANCES IN KNOWLEDGE
Demonstrates the frequency, location and underlying diagnosis of pathological fractures in paediatric bone tumour and tumour-like lesions.
Topics: Adolescent; Bone Neoplasms; Bone and Bones; Child; Child, Preschool; Diagnosis, Differential; Female; Fractures, Spontaneous; Humans; Image-Guided Biopsy; Infant; Male; Radiography; Retrospective Studies
PubMed: 34319796
DOI: 10.1259/bjr.20201341 -
International Journal of Hematology Dec 2023Myeloid sarcoma is a rare clinical entity that presents as an isolated proliferation of leukemic cells, concurrently with or at relapse of acute myeloid leukemia (AML),... (Review)
Review
Myeloid sarcoma is a rare clinical entity that presents as an isolated proliferation of leukemic cells, concurrently with or at relapse of acute myeloid leukemia (AML), myelodysplastic syndromes/neoplasms (MDS), chronic myeloid leukemia (CML), and myeloproliferative neoplasm (MPN). Myeloid sarcoma disrupts the normal architecture of its surrounding tissues. When it forms in long bones, it can cause their pathological fracture. We recently experienced a rare case of MDS presenting with myeloid sarcoma in the femur that eventually resulted in its pathological fracture. Detailed chromosomal analysis of the bone marrow cells suggested emergence of myeloid sarcoma during the fast-paced progression of MDS just after acquiring trisomy 22. A comprehensive review of previous cases of myeloid sarcoma-associated pathological fracture indicated possible involvement of structural rearrangements of chromosomes 9 and 22. Management of myeloid sarcoma should continue to improve, and clinicians should note that myeloid sarcoma with specific chromosomal alterations needs extra medical attention to prevent pathological fracture.
Topics: Humans; Sarcoma, Myeloid; Fractures, Spontaneous; Myeloproliferative Disorders; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute
PubMed: 37707761
DOI: 10.1007/s12185-023-03656-1 -
The Pan African Medical Journal 2021
Topics: Bone Neoplasms; Fractures, Spontaneous; Humans; Osteolysis
PubMed: 34754357
DOI: 10.11604/pamj.2021.39.280.25695 -
Medicine Aug 2022Primary hyperparathyroidism (PHPT) with pathological fracture is rare, and the early symptoms of PHPT lack specificity, leading to misdiagnosis. Therefore, this study... (Observational Study)
Observational Study
Primary hyperparathyroidism (PHPT) with pathological fracture is rare, and the early symptoms of PHPT lack specificity, leading to misdiagnosis. Therefore, this study aimed to summarize the clinical characteristics and treatment of PHPT patients with pathological fractures and to improve the attention of orthopedic clinicians to PHPT. It is a retrospective study, 2226 patients with hyperparathyroidism in our hospital from 2009 to 2019 were screened, excluding secondary hyperparathyroidism and patients without limb fracture, and the remaining 20 patients with PHPT accompanied by pathological fractures were finally analyzed. Parathyroid hormone (PTH) and calcium levels were compared on the first postoperative day, and the prognosis of the patients was assessed by bone mineral density and Visual Analogue Scale scores at 3 and 12 months postoperatively. The early symptoms of PHPT patients in this study included urinary calculi (80%), bone pain (30%), and digestive tract symptoms (25%). Fourteen (70%) cases were misdiagnosed at the initial diagnosis. After parathyroidectomy, the blood calcium and PTH levels decreased significantly in all patients (P < .05). For the treatment of fracture, 9 of the patients underwent surgical treatment of the fracture, while the remaining patients received splint external fixation. The follow-up time was 4.60 ± 0.62 years (1-10 years). All patients recovered well from the fracture, the symptoms of systemic bone pain were markedly improved, and bone mineral density was significantly improved after surgery. Orthopedic surgeons need to avoid misdiagnosis and pay attention to the early symptoms in PHPT patients with pathological fracture, and better therapeutic effects can be obtained by combining parathyroidectomy with fractures fixation.
Topics: Bone Density; Calcium; Fractures, Bone; Fractures, Spontaneous; Humans; Hyperparathyroidism, Primary; Pain; Parathyroid Hormone; Parathyroidectomy; Retrospective Studies
PubMed: 35984170
DOI: 10.1097/MD.0000000000029966 -
Journal of Orthopaedic Research :... Jun 2020Metastatic breast, prostate, lung, and other cancers often affect bone, causing pain, increasing fracture risk, and decreasing function. Management of metastatic bone... (Review)
Review
Metastatic breast, prostate, lung, and other cancers often affect bone, causing pain, increasing fracture risk, and decreasing function. Management of metastatic bone disease (MBD) is clinically challenging when there is potential but uncertain risk of pathological fracture. Management of MBD has become a major focus within orthopedic oncology with respect to fracture and impending fracture care. If impending skeletal-related events (SREs), particularly pathologic fracture, could be predicted, increasing evidence suggests that prophylactic surgical treatment improves patient outcomes. However, current fracture risk assessment and radiographic metrics do not have high accuracy and have not been combined with relevant patient survival tools. This review first explores the prevalence, incidence, and morbidity of MBD and associated SREs for different cancer types. Strengths and limitations of current fracture risk scoring systems for spinal stability and long bone fracture are highlighted. More recent computed tomography (CT)-based structural rigidity analysis (CTRA) and finite element (FE) analysis methods offer advantages of increased specificity (true negative rate), but are limited in availability. Other fracture prediction approaches including parametric response mapping and positron emission tomography/computed tomography measures show early promise. Substantial new information to inform clinical decision-making includes measures of survival, clinical benefits, and economic analysis of prophylactic treatment compared to after-fracture stabilization. Areas of future research include use of big data and machine learning to predict SREs, greater access and refinement of CTRA/FE approaches, combination of clinical survival prediction tools with radiographically based fracture risk assessment, and net benefit analysis for fracture risk assessment and prophylactic treatment.
Topics: Bone Neoplasms; Clinical Decision-Making; Finite Element Analysis; Fractures, Spontaneous; Humans; Morbidity; Risk Assessment; Tomography, X-Ray Computed
PubMed: 32162711
DOI: 10.1002/jor.24660