The osteoclast—what’s new?

Bone resorption is required for skeletal modelling during bone growth and for mineral homeostasis and bone remodelling throughout life. Osteoclasts are multinucleated cells that are uniquely specialised to carry out this physiological bone resorption. As osteolysis is a feature of most diseases of bone and joint, osteoclasts also play a role in pathological bone resorption, the extent of which is a function of the cellular and molecular mechanisms that govern their formation and function.     

Clinical utility of biochemical marker of bone remodelling in patients with bone metastases of solid tumors.

Bone turnover is characterized both by the formation of new bone by the osteoblasts and the resorption of old tissue by the osteoclast. This process takes place only on the surface of bone and can be described in terms of spatio-temporal events that are the bone metabolic unit and the bone remodelling cycle. The former consists of a discrete group of cells (osteoblasts and osteoclasts) involved in a particular remodelling event while the latter represents the succession of resorption and formation. In a typical remodelling cycle, resorption takes 7-10 days, whereas formation requires 2-3 months. Remodelling is regulated either by local or systemic factors, including electrical and mechanical forces, hormones (e.g. parathyroid hormone, sexual steroids, calcitriol, cortisol, thyroid hormones, calcitonin), growth factors and cytokines. Recently different circulating biochemical markers have been proposed for the investigation of bone turnover. In addition to classical parameters such as serum alkaline phosphatase and urinary calcium and hydroxyproline, new markers have gained clinical attention because of their accuracy in assessing the dynamic changes in bone remodelling (bone alkaline phosphatase, osteocalcin, propeptides PICP and PINP, tartrate-resistant acid phosphatase, deoxypyridinoline, pyridinoline, telopeptide CTx and NTx). The aim of this review is to present the recent advances in this field and the clinical application of markers of bone turnover in patients with bone metastases from solid tumors. Also the cellular and molecular bases of bone remodelling are reported with details.     

创伤后骨质溶解症X线图像特征

目的 探讨创伤后骨质溶解症的X线表现,提高对该病认识.方法 回顾性分析经临床、病理证实的7例创伤后骨质溶解症X线表现.7例中女5例,男2例.年龄9～56岁,平均34岁.车祸3例,摔伤4例.受伤后距骨质溶解时间分别为18个月1例,10个月2例,6个月2例,3个月2例.结果 受伤时X线示坐、耻骨骨折2例,胫腓骨下段骨折1例,股骨颈骨折1例,肱骨外科颈粉碎性骨折1例,肩锁关节Ⅰ度脱位1例,腕部软组织肿胀1例.X线表现为块状骨质溶解3例,斑片状骨质溶解3例,囊状骨质溶解1例;溶解边缘骨质均无硬化,其中溶解区界限清楚5例,界限不清楚2例;溶解区无残留骨组织4例,残留部分骨组织3例;溶解区附近骨质均未见骨膜增生和骨皮质增厚;骨质修复2例,溶解骨质无修复5例.病理检查显示病变区见大量毛细血管和纤维组织增生,滑膜充血肿胀、增生,肉芽组织增生,骨坏死,破骨细胞活跃,少量炎性细胞,无肿瘤细胞.结论 创伤后骨质溶解症与外伤密切相关,X线表现为块状和斑片状骨质溶解或不规则骨质囊状破坏,早期诊断较难.     

Severe osteolysis and soft tissue mass around total hip arthroplasty: description of four cases and review of the literature with respect to clinico-radiographic and pathologic differential diagnosis

Periprosthetic osteolysis is a well known phenomenon caused by wear particle-induced bone resorption, particularly common and extensively reported in total hip arthroplasty. Its typical radiographic feature is a radiolucent area adjacent to an implant, sometimes associated with a soft tissue mass. Osteolytic changes may be caused by numerous other pathologic processes, including infection, metabolic disease, and neoplasia. Four cases of massive periprosthetic bone destruction associated with a large soft tissue mass around a failed total hip replacement are presented. In three cases, a diagnosis of periprosthetic osteolysis was correctly made and managed by revision surgery. However, in one case angiosarcoma of the ipsilateral hemipelvis went long unrecognized despite aggressive clinical course, requiring hind-quarter amputation and ultimately resulting in the patient's death. Periprosthetic malignancy in the form of either primary sarcoma or metastatic cancer is a very rare yet reported event in the setting of previous hip replacement, likely leading to catastrophic consequences when diagnosis is not established in a timely manner. The differential diagnosis of periprosthetic osteolysis should consider the entire spectrum of conditions that can present with radiolucent changes. Thorough review of patient's history and course of symptoms, along with careful evaluation of standard roentgenograms should be always performed and possibly integrated with imaging modalities such as CT, MRI, and bone scintigraphy in order to increase diagnostic accuracy. If uncertainty remains, biopsy should always be considered to rule out malignancy.     

Relative accretion of 99mTc-polyphosphate by forming and resorbing bone systems in rats: its significance in the pathologic basis of bone scanning.

The relative roles of osteogenesis andd osteolysis in the production of positive radionuclide images of skeletal lesions were investigated. The uptake of 99mTc-polyphosphate (Tc-PP) by each process was measured in an animal model that permitted bone formation and resorption to be studied independently. Ten rats received intramuscular implants of bone-forming demineralized matrix (DM) and resorbing devitalized bone (DV). Radiographs and Tc-PP scintiscans were made each week thereafter. At 6-10 weeks, the implants and normal bone samples were removed, counted for 99mTc, and examined histologically. The uptake of Tc-PP BY DM implants was first detected on images made 3 weeks after implanatation, and by DV implants, 1-2 weeks later. Serial radiography showed progressive calcification of DM an resorption of DV implants. Microscopic examinations of undecalcified sections, stained with a modified Goldner preparation, revealed vital-bone formation in the DM implants and osteoclastic resorption in the DV. Activity counts per gram of DM and DV implants were, respectively, 200% and 90% that of normal bone. Since only the bone-forming system (DM) accumulated Tc-PP at greater than normal concentrations, this study indicates that positive bone images of osteolytic lesions solely reflect compensatory osteogenic responses.     

Stress fracture of the tarsal navicular

Stress fractures of the lower extremity are common among military members and athletes at all levels of participation. They typically occur when an individual begins a new or different type of physical training or during periods of abrupt increase in the level of training. Stress fractures represent an incomplete remodeling of bone that occurs secondary to repetitive mechanical loading. In response to this increased loading, the osteoclastic resorption of lamellar bone outpaces the ability of the osteoblasts to create new lamellar bone, eventually leading to structural failure. The following case report reviews the typical clinical presentation, imaging findings, and treatment of the tarsal navicular stress fracture.     

Seventeen year follow-up and autopsy findings in a case of massive osteolysis

Clinical, radiologic, and pathologic findings in an unusual case of massive osteolysis are described. Peculiar clinical episodes of a foul body odor with fever and erythematous skin lesions, presence of radiographic findings such as acro-osteolysis and periarticular erosions, and the absence of angiomatous or lymphangiomatous dysplasias at autopsy, indicate that this is a new form of massive osteolysis rather than a variant of Gorham disease.     

Radiologic findings in Gorham-Stout syndrome

Gorham-Stout syndrome, also called "disappearing bone disease" or idiopathic massive osteolysis, is a rare disease of unknown etiology and pathogenesis. It is characterized by rapidly progressive localized massive osteolysis associated to a proliferation of vascular structures of benign origin in which the absence of new bone formation is representative. We present two cases (a six-year-old boy with affected right ulna, and a 15-year-old girl with right rib affection associated to chylothorax) of this disease with the characteristic clinical, histological, and imaging findings.     

巴戟天甲基异茜草素对破骨细胞性骨吸收的影响

目的研究甲基异茜草素抑制骨吸收的细胞学机制。方法采用原代培养的成骨细胞和骨髓单核细胞联合培养的方法,在1,25-（OH）2VitaminD3和地塞米松作用下,使骨髓单核细胞分化形成破骨细胞。磷酸苯二钠法测定破骨细胞抗酒石酸酸性磷酸酶（Tartrate-resistant acid phosphatase,TRAP）的活性;计算机图像分析技术测定骨片上破骨细胞性骨吸收陷窝的面积;荧光酶标方法测定组织蛋白酶K的活性。结果甲基异茜草素在0.1～10μmol·L^-1范围内,浓度依赖性地抑制破骨细胞形成、分化、TRAP酶活性和在骨片上形成的吸收陷窝的数目和面积。结论甲基异茜草素通过抑制破骨细胞的形成、分化和骨吸收功能来减少骨质的丢失。     

The radiographic features of familial expansile osteolysis

The radiographic features of a unique autosomal dominant bone dysplasia are presented. The features are classified as generalised and/or focal. Generalised features are either altered trabecular pattern or modelling abnormalities. Focal features comprise lytic areas which progressively enlarge, producing expansion of the bone and eventual disintegration due to fibrous and finally fatty replacement of the normal medulla. Almost 90% of these lesions occur in the appendicular skeleton. Clinically, hearing loss is the earliest manifestation of the disease, presenting sometimes as early as 4 years of age. Apical and cervical resorption of teeth is extremely common, resulting in premature loss of teeth. Radiologically, the differential diagnosis refers to Paget's disease, polyostotic fibrous dysplasia, and osteofibrous dysplasia. The progressive destruction of the bone is similar to massive osteolysis (Gorham's disease). The radiographic features in combination with the histopathology render the condition unique.     

Carpal-tarsal osteolysis with elbow involvement

Carpal-tarsal osteolysis is a rare condition that manifests as the progressive resorption of carpal and tarsal bones in young children. The diagnosis of this condition is often difficult and delayed as the initial clinical presentation is non-specific. Radiographic changes occur gradually, are often not seen at presentation and depend on recognising loss of bone in the ossification centres of the carpus and tarsus. MRI demonstrates morphological abnormalities in the cartilaginous, as well as the osseous components, of the developing carpal and tarsal bones and therefore may be helpful in predating the radiographic changes. Ultrasound appears to contribute little to the diagnosis and may be misleading. Exclusion of other conditions, particularly juvenile idiopathic arthritis, is important in making the diagnosis. MRI can be useful in excluding an inflammatory arthropathy, and suggesting the diagnosis of carpal-tarsal osteolysis.     

The mode of progression of subperiosteal resorption in the hyperparathyroidism of chronic renal failure

Subperiosteal resorption in finger phalanges is usually thought to be the result of osteoclastic bone resorption on the periosteal surface of bone, progressive centripetally, with creation of the serrated appearances and “lace-like” patterns in periosteal cortical bone. Our longitudinal microradioscopic observations in patients with secondary hyperparathyroidism of chronic renal failure have revealed evidence of another pathogenetic mechanism: by the enlargement of intracortical juxtaperiosteal resorption spaces, the remaining thin layer of bone is broken down from inside the bone, i.e., a centrifugal rather than centripetal process.     

Radioactive iodine treatment in medullary thyroid carcinoma

BACKGROUND: Elevated levels of basal and stimulated calcitonin are commonly seen in hereditary and sporadic medullary thyroid cancer (MTC) following total thyroidectomy. The cause of these high levels can be residual thyroid tissue, possibly with C-cell hyperplasia, and/or residual micro-MTC foci. MTC does not have the ability to concentrate radioactive iodine. However, radioactive iodine trapped by thyroid follicular cells may affect the neighbouring parafollicular cells. AIM: To investigate the effect of radioactive iodine treatment as adjuvant therapy to surgery in seven patients with persistent elevation of basal and stimulated calcitonin levels. METHODS: Pentagastrin testing was performed in each case immediately before surgery and at intervals of 6 months over a maximum period of 5 years (range, 44-60 months) after surgery. RESULTS: A significant decrease in basal and stimulated calcitonin levels was observed in three patients whose disease was localized to the thyroid gland at the final visit. In the remaining four patients, who initially had lymph node involvement at surgery, basal and stimulated calcitonin levels were decreased significantly in only one. At follow-up, of the three patients who showed no decrease in basal and stimulated calcitonin levels, two developed further regional lymph node and distant metastases. CONCLUSIONS: In patients with persistently elevated basal and stimulated calcitonin levels, radioactive iodine treatment may be the therapy of choice for C-cell hyperplasia and/or micro-MTC after optimal thyroid surgery, especially if the disease has not spread beyond the thyroid gland.     

Ultrasound evaluation of inflammation in patients with chronic recurrent multifocal osteomyelitis involving the mandible: report of three cases

Chronic recurrent multifocal osteomyelitis (CRMO) is aseptic and can be diagnosed by excluding other diseases, such as bacterial osteomyelitis, scurvy, metabolic disorders, and malignant diseases; therefore, bone biopsy is usually performed to confirm the diagnosis. To prevent misdiagnosis, the appropriate timing and location for biopsy should be determined from an active phase of inflammation. We presented 3 cases of CRMO involving the mandible: Case 1: A 2-year-old girl diagnosed with CRMO in the chronic phase. A sonogram showed a slightly low echoic area adjacent to the bone cortex. Pathological examination revealed a slight accumulation of leukocytes and plasma cells, as well as predominant fibrous stroma. Case 2: A 9-year-old girl diagnosed with CRMO with massive new osteoid formation. A sonogram showed a massive inhomogeneous low echoic area adjacent to the bone cortex. Pathological examination revealed massive osteoid formation and scattered inflammatory cells infiltration. Case 3: A 3-year-old girl diagnosed with CRMO in the active phase. A sonogram showed a massive hypoechoic area adjacent to the bone cortex and hyperechogenicity associated with a muscular and subcutaneous edema. Pathological examination revealed massive bone destruction and neutrophils infiltration within damaged osteoid. Ultrasound was able to visualize the degree of inflammation in the mandible corresponding to that of the surrounding soft tissue in all 3 cases. Therefore, ultrasound would be useful in determining the appropriate timing and location for bone biopsy.     

The pathology of total joint arthroplasty

Although the clinical results of total joint arthroplasty are usually excellent, some implants develop loosening and require revision. Implants usually fail by a combination of mechanisms, but different basic designs tend to show different dominant mechanisms of failure. Infection causes failure of about 1–5% of cases of primary arthroplasty. Clues to the presence of infection include clinical signs, a periosteal reaction, a positive culture of aspirated joint fluid, and acute inflammation identified in tissue around the implant. There are several different mechanisms and modes of implant wear, and perhaps the most important cause of aseptic loosening is an inflammatory reaction to particles of wear debris. Abrasive, adhesive, and fatigue wear of polyethylene, metal and bone cement produces debris particles that induce bone resorption and implant loosening. Particles can cause linear, geographic, or erosive patterns of bone resorption (osteolysis), the distributions of which are influenced by the implant design. Micromotion of implants that did not achieve adequate initial fixation is another important mechanism of loosening. Fatigue failure at the bone/cement and bone/implant interface may cause aseptic loosening, and may be especially important for implants with relatively smooth surfaces. Stress shielding can influence local bone density, but is rarely an isolated cause of implant loosening. Elevated hydrodynamic pressure has been associated with bone resorption in the absence of implants, and may also play a role in implant loosening. Received: 29 March 1999 Revision requested: 5 May 1999 Revision received: 7 June 1999 Accepted: 9 June 1999     

激素替代治疗与绝经后骨质疏松症

绝经后骨质疏松症主要是由于卵巢功能的减退或衰竭、雌激素水平下降而导致破骨细胞的骨吸收大于成骨细胞的骨形成,以进行性骨丢失、骨小梁退行性病变、骨质疏松、骨脆性增加和骨折风险增加为临床特征的全身性疾病,具有发病率随绝经年限延长而增高的特点。临床中相当数量的绝经后女性并不重视骨质疏松的严重性,从而延误了预防和治疗的最佳时机,增加了骨质疏松症治疗的复杂性。激素替代治疗是预防和治疗绝经后女性骨质疏松的有效方法之一,尤其是对于预防过早绝经妇女的骨质丢失已成为一线的治疗手段,且具有成本低、安全性高的优点。激素替代治疗不仅可增加患者的骨密度、减缓骨丢失,而且还可使血清降钙素、碱性磷酸酶骨质破坏的标志物较基础水平明显下降,起到预防和治疗绝经后妇女骨质疏松和骨折的作用。本文就绝经后妇女骨质的改变进行综述。     

Gorham’s disease of the radius: radiographic, scintigraphic, and MRI findings with pathologic correlation

A rare case of Gorham’s disease affecting the radius in a 46-year-old woman is presented. It was studied by plain radiography, MRI, and scintigraphy, including three-phase radionuclide bone scan and thallium scan. Three-phase bone scan demonstrated slightly decreased activity in the affected portion of the forearm in the early phase, but showed increased activity on the blood pool and delayed imaging. A thallium scan revealed no abnormalities. Histopathologic examination revealed osteoclastic activity and scar tissue with minimal remaining vasculature.     

A Case of an Idiopathic Massive Osteolysis with Skip Lesions

A patient with a 2-year history of pain in the left arm, and decreased strengths unrelieved by non-steroidal anti-inflammatory therapy, was being referred for repeating radiography. The radiologic examinations have demonstrated a unique pattern of non-contiguous osteolysis in the left elbow, proximal and distal radius, ulna, wrist, carpal bones, proximal and distal metacarpals and phalanges. Multi-site biopsies were being performed and confirmed the diagnosis of massive osteolysis. To our knowledge, this is the first case in which multifocal, non-contiguous osteolysis with skip lesions without associated nephropathy and without a hereditary pattern is being described in one extremity.     

Thyroid carcinoma with biphasic clinical course and evolution in medullary carcinoma-follicular variant. A case report and an immunocytochemical demonstration of calcitonin and thyroglobulin in the same neoplastic cells

The authors present an unusual case of thyroid neoplasia firstly diagnosed as an anaplastic carcinoma with no rise in plasma thyroglobulin (Tg) and treated with total thyroidectomy and radioiodine administration. After 18 months regional lymph node metastases were present with a rise in plasma calcitonin (Ct) (8000-14000 pg/ml); lymphectomy and external radiation were performed and histology revealed a metastasis from thyroid medullary carcinoma. After 3 years, mediastinal and right supraclavicular masses were present with a concomitant rise in plasma calcitonin (from 700 to 3400 pg/ml); all neoplastic lesions showed radioiodine uptake and plasma Tg was 8.9 ng/ml. A biopsy of the supraclavicular region was taken and 131I therapy was attempted, but the patient died after 6 months. Immunocytochemistry of the biopsy revealed the presence of a medullary carcinoma-follicular variant: the neoplastic cells were variably reacting with anti-Ct and anti Tg, and, moreover, the two antigens were sometimes observed in the same cell bodies. The metabolic pattern and the clinical course of this tumour are discussed, and the authors propose that Ct and Tg plasma levels be evaluated and a total body scan (WBS) with radioiodine be performed in all cases of medullary or poorly differentiated thyroid carcinomas.     

Severe metallosis after unicompartmental knee arthroplasty

We report on a case of a patient who had femoral osteolysis and severe metallosis of the knee joint resulting from the secondary abrasive wear of the metal-backed tibial component of a unicompartmental knee arthroplasty due to massive wear of tibial polyethylene. The failure was diagnosed 11 years after implantation. This metallosis affected the intra-articular tissues and the subchondral bone.