Hydroxyapatite crystals as a bone graft substitute in benign lytic lesions of bone

Background:

Bone grafts are required to fill a cavity created after curettage of benign lytic lesions of the bone. To avoid the problems associated at donor site with autologous bone graft, we require allograft or bone graft substitutes. We evaluated the healing of lytic lesions after hydroxyapatite (HA) grafting by serial radiographs.

Materials and Methods:

Forty cases of benign lytic lesions of bone were managed by simple curettage and grafting using HA blocks. Commercially available HA of bovine origin (Surgiwear Ltd., Shahjahanpur, India) was used for this purpose. Mean duration of followup was 34.8 months (range 12–84 months). Mean patient age was 19.05 years (range 3–55 years). Radiological staging of graft incorporation was done as per criteria of Irwin et al. 2001.

Results:

In our series, two cases were in stage I. A total of 11 cases were in stage II and 27 were in stage III. Graft incorporation was radiologically complete by 15 months. Clinical recovery was observed before radiological healing. The average time taken to return to preoperative function was 3 months. Recurrence was observed in giant cell tumor (n = 3) and chondromyxoid fibroma (n = 1). There was no incidence of graft rejection, collapse, growth plate disturbances or antigenic response.

Conclusions:

We conclude that calcium HA is biologically acceptable bone graft substitute in the management of benign lytic lesions of bone.     

Surgical treatment of lymph nodes with metastatic melanoma from unknown primary site

To determine the prognosis of patients with lymph node metastases from an unknown primary melanoma, we retrospectively reviewed the clinicopathologic features of 188 such patients treated from 1971 through 1986 and compared their records with those of patients with clinical stage II melanoma with known primary lesions. Patients with lymph node metastases from an unknown primary melanoma represented 4.6% of all patients with melanoma treated during that period. The five- and ten-year survival rates were 42% and 40%, respectively (median, 37 months). When stratified by number of tumor-containing lymph nodes, there was no significant difference in survival between patients with an unknown primary melanoma and lymph node metastases and those with clinical stage II melanoma and known primary sites. The prognosis of the former patients is no worse than that of patients with lymph node metastases from a known primary site and should be treated in a comparable manner.     

Surgical treatment of metastatic bone disease of the distal extremities

Metastatic bone disease of the distal extremities, also known as acrometastasis, is very rare. Thus, there is very limited information regarding the clinical manifestations and methods of surgical treatment. The current available literature shows that acrometastases are often encountered in the context of advanced disease and are thus associated with poor patient survival. As metastatic bone disease is generally uncurable, the goal of surgical treatment is to provide the patient with good function with as few complications as possible. In this article, we discuss the clinical manifestation of acrometastases, the methods of surgical intervention, and the expected clinical outcome. Non-surgically managed pathological fractures generally remain ununited; therefore, conservative treatment is reserved for patients with poor general condition or dismal prognosis. The current evidence suggests that in lesions of the lower arm and leg, osteosynthesis(plate and screw fixation or intramedullary nail) is the most common method of reconstruction, whereas local excision or amputation are more commonly used in cases of more distal lesions(such as ankle, foot and hand). Following surgery most patients receive adjuvant radiotherapy, even though its role is poorly documented. Close collaboration between orthopedic surgeons and medical oncologists is necessary to improve patient care and treatment outcome. Further studies are needed in order to provide stronger clinical evidence and improve decision-making, in an effort to optimize the patients' quality of life and avoid the need for revision surgery.     

Clinical outcome of percutaneous osteoplasty for pain caused by metastatic bone tumors in the pelvis and femur

We examined the pain-relieving effects in five patients who underwent percutaneous osteoplasty (POP) for pain caused by metastatic bone tumors in the pelvis and femur. Pain intensity, improvement of walking, and complications associated with POP were evaluated. Pain was measured using a numerical rating scale (NRS), with scores ranging from 0 (no pain) to 10 (worst pain imaginable). The patients were four men and one woman (mean age, 65 years). POP was performed in the pelvis in three patients and in the femur in two patients. Three of the subjects had already received radiation therapy at the lesion. The scores on the NRS on moving in the five patients before POP were 5, 8, 5, 4, and 7. After POP, the NRS scores decreased to 0, 0, 2, 0, and 1, respectively, within 72 hs. Three of the patients showed improvements in walking. There were no complications associated with POP. However, pathological fracture occurred, while walking, 4 days after POP in one patient. Percutaneous osteoplasty is a safe and effective treatment for pain caused by metastatic bone tumors in the pelvis and femur. However, care and attention should be paid to the risk of pathological fracture after POP of the femur.     

Treatment modalities for metastatic bone tumors and associated issues: focusing on surgical indications and techniques for metastatic lesions in limb bones

Metastatic bone tumors are traditionally the most commonly encountered form of malignant bone tumor. In recent years, the prevalence of metastatic bone tumors has shown a tendency of further increase, due to advances in cancer treatments that prolong survival. Accompanying this increase, the chances that orthopedic surgeons will encoun-ter these tumors and the need for surgical treatment are increasing. Metastatic bone tumor usually constitutes only part of the metastatic lesions. Although local control at the bone metastatic site alone may have little effect on the total curability, the quality of life (QOL) of the patient cannot be ensured if local control is ignored. Therefore it is important to achieve local control by interdisciplinary treatments aiming at reduced surgery and at functional conservation. Received: November 9, 1999     

Bisphosphonates in Breast Cancer Patients with Bone Metastases

Morbidity and mortality in breast cancer patients are mainly caused by organ failure as a result of distant metastasis. The main target of metastatic disease is the skeleton (next to lungs and liver). Osseous metastases are diagnosed in 75-80% of all women who die due to breast cancer; and the skeleton is the primary metastatic target organ in more than half of these cases. In Germany, the incidence of breast cancer patients with newly diagnosed bone metastases is approximately 11-12,000 cases. Prevalence might amount to 40,000 cases of women with breast cancer and osseous metastases at a median survival time of 3-4 years. The treatment goal at this stage of the disease comprises improvement of quality of life, and reduction of bone pain and typical complications like fractures and hypercalcemia. By consistent use of bisphosphonates these goals can be accomplished. Bisphosphonates improve bone pain significantly and reduce the number of skeletal-related events in women with bone metastases. Bisphosphonates can be administered intravenously or orally, and are well tolerated. Nevertheless, there are side effects and complications including acute phase reaction, nephrotoxicity, osteonecrosis of the jaw, and gastrointestinal disturbances.     

Spinal stabilization for patients with metastatic lesions of the spine using a titanium spacer

Summary Anterior decompression in spinal metastases of the corporal type with impending (n=5) or present (n=36) neurological complications was performed in 41 patients. For reconstruction, a titanium cylinder was inserted after spondylectomy and augmented with an anterior plate. The titanium implant can easily be adjusted to the length needed without necessitating expensive additional equipment. Outside the patient the implant is filled with polymethylmetacrylate, facilitating plate transfixation for rotational locking. There was a 30-day mortality of 9.7%. Pain relief was apparent in 38 of 41 patients (92.7%), and motor improvement was manifest in 31 of 35 cases (88.6%). Six patients did not present with any neurological symptoms pre- or postoperatively. Neurological deterioration was registered in only 1 case (2.4%). Surgical efficacy was maintained until the death of the patients. Though tumor recurrence at a different spinal level led to consecutive surgery in 5 patients, no implant dislocation occurred during the observation period (maximum 44 months), characterizing the procedure as a mechanically reliable and safe technique.     

The effect of intravenous pamidronate versus oral alendronate on bone mineral density in patients with osteoporosis

Intravenous pamidronate is frequently used for the treatment of osteoporosis in patients who cannot tolerate oral bisphosphonates. The aim of the present study was to compare the changes in bone mineral density (BMD) after 1 year of treatment with either oral alendronate or intravenous pamidronate in patients with osteoporosis. We studied 40 consecutive patients starting treatment for osteoporosis: 20 received oral alendronate 10 mg/day and 20 received intravenous pamidronate 60 mg/3 months. Patients were started on intravenous pamidronate in the case of intolerance (within 1 month of start of treatment) of an oral bisphosphonate or in the case of contraindications for an oral bisphosphonate. BMD (spine and total hip) was measured with dual X-ray absorptiometry (DEXA) at the start of treatment and after 1 year. The BMD of the lumbar spine increased by 4.0% (P<0.05 vs baseline) in both groups, and the BMD of the hip increased by 3.3% and 2.9% (P<0.05 vs baseline) in the alendronate and pamidronate groups, respectively. The increases in BMD of the vertebral spine and the total hip after 1 year are comparable in the alendronate and pamidronate groups. We conclude that intravenous pamidronate can be used successfully as an alternative treatment in patients with gastrointestinal intolerance of an oral bisphosphonate.     

The clearance and bioavailability of pamidronate in patients with breast cancer and bone metastases

Summary The pharmacokinetics and bioavailability of pamidronate were assessed in patients with breast cancer, 6 subjects received the drug intravenously and 7 orally. The initial plasma half-life of pamidronate was short (42±27 min) and the apparent total plasma clearance was high (471±298 ml/min). The renal clearance (74±34 ml/min) was similar to the creatinine clearance (66±19 ml/min). Most of the renal elimination occurred during and immediately post a 4 h infusion of the drug (23.2±7.9% in 24h). The non-renal clearance was ascribed to uptake by bone and deep tissue compartments. Little additional drug appeared in the urine after 24 h. The mean bioavailability was estimated using a parallel study design to be 0.3% for a 300 mg oral dose.     

Differential action of pamidronate on trabecular and cortical bone in women with involutional osteoporosis

Since osteoporotic fractures are mainly related to the diminution of the bone mineral density (BMD), the effect of pamidronate (3-amino-1-hydroxy-propylidene) 1,1-bisphosphonate on the BMD of the spine, proximal femur and radius shaft was evaluated in an initial cohort of 35 postmenopausal women with at least one vertebral fracture due to involutional osteoporosis.Pamidronate was given continuously during 18 months in a daily oral dose of 4.8 to 6.0 mg/kg supplemented with calcium (1 g/day).BMD — measured by dual photon absorptiometry — increased after one year 5.3±1.0% (P<0.001) in lumbar spine and 5.3±1.5% (P<0.001) over trochanter. However no significant changes were observed in the BMD of the femoral neck, Ward's triangle or in the cortical bone of the radius shaft measured by single photon absorptiometry.Pamidronate also decreased significantly urinary hydroxyproline-creatinine excretion after 6 months and thereafter maintained a plateau. After 18 months of treatment the diminution was 42.6±4.9% (P<0.001).The differing effects of pamidronate on the BMD of lumbar spine and proximal femur might be ascribed to dissimilarities between the proportions of trabecular and cortical bone in these. These results suggest that pamidronate may be prescribed to prevent fractures in cases of involutional osteoporosis with a significant decrease of BMD in lumbar spine and/or trochanter.     

Pamidronate increases markers of bone formation in patients with multiple myeloma in plateau phase under interferon-alpha treatment

Bisphosphonates are potent inhibitors of osteoclastic activity and reduce the disease-related skeletal complications when they are used in combination with chemotherapy in patients with multiple myeloma (MM). Pamidronate also inhibits apoptosis of primary osteoblastic cells and probably induces apoptosis on human MM cells and osteoclasts. It has been reported that interferon-alpha (IFN-α) decreases bone resorption and that low doses of IFN-α result in a significant increase in serum osteocalcin (OSC). The aim of this study was to determine the effects of pamidronate treatment on biochemical markers of bone resorption [cross-linked N-telopeptides of type I collagen (NTx)], bone formation [bone alkaline phosphatase (BAP) and OSC], disease activity [β₂-microglobubin, CRP, paraprotein], and interleukin-6 (IL-6) in patients with MM in plateau phase under IFN-α maintenance. The above parameters were evaluated in 28 patients (13 M, 15 F, median age 70 years) during maintenance treatment, before the addition of pamidronate and after 1, 3, 6, 9, 12, and 14 months of the combined therapy. The addition of pamidronate to maintenance treatment resulted in a significant reduction of NTx, IL-6, β₂-microglobulin, CRP from the 3^rd month and para-protein from the 6^th month of treatment, whereas BAP and OSC were significantly increased from the 6^th month. These changes continued during the 14-month follow-up of the combined treatment. Multivariate analysis showed a significant negative correlation between changes of BAP and OSC and the patients' age. The greater increase of the bone for-mation markers was observed in younger patients. These results suggest that, in addition to the inhibition of osteoclastic activity, pamidronate in combination with IFN-α was shown to induce bone formation in patients with MM in the plateau phase.     

寡转移CRPC原发灶与转移灶全覆盖放疗的疗效和毒性反应分析

目的:探讨原发灶和所有转移灶同时全覆盖放疗治疗寡转移性去势抵抗性前列腺癌(CRPC)的疗效和毒性反应。方法:回顾性分析北京大学第一医院2011年10月至2017年6月收治的44例寡转移(≤4处转移灶)CRPC患者的临床资料。平均年龄72(57~86)岁,初诊时PSA中位值38.545(6.640~1 066.000)n...     

Treatment of chronic recurrent multifocal osteomyelitis with bisphosphonates in children

ObjectivesAssessment of bisphosphonates efficiency in the therapy of NSAIDs-refractory Chronic Recurrent Multifocal Osteomyelitis.MethodsRetrospective analysis of records of patients treated for Chronic Recurrent Multifocal Osteomyelitis between 2012 and 2018.ResultsBetween 2012 and 2018, 76 children and adolescents were diagnosed with Chronic Recurrent Multifocal Osteomyelitis in our department. All patients underwent an initial course of NSAIDs therapy that provided a remission in 46% of cases. Of 41 NSAIDs-resistant cases, 7 patients were male and 34 were female. Disease started meanly in the age of 10. Most frequently pain localised in foot, clavicle and hip. In presented group, pamidronate was administered intravenously in the dose of 1 mg/kg/day for 3 days. Patients received 6 series (1–17 series) on average with mean interval of 10 weeks (4–14 weeks). Our observations demonstrated rapid decrease of symptoms intensity after first dose of pamidronate with relapse of pain after 3–4 weeks. The frequency of pamidronate dosage was dependent of patient's symptoms. No serious adverse effects were reported. We finished the therapy after complete remission of symptoms and complete bone remodelling in imaging. Of 41 patients, 32 achieved remission and 9 continue their therapy. In remission group patients received 7 series of pamidronate on average and their treatment lasted meanly 20 months.ConclusionsPamidronate is a safe and efficient method of CRMO therapy, particularly in cases refractory to NSAIDs treatment. Treatment with pamidronate provides both symptomatic relief as well as normalisation of bone morphology.     

胸腰椎转移瘤后路手术中骨水泥的应用

目的:探讨骨水泥在胸腰椎转移瘤后路手术中的应用价值.方法:2004年3月～21208年12月,后方入路手术治疗胸腰椎转移性肿瘤患者26例,原发肿瘤:肺癌9例,乳腺癌7例,肝癌4例,前列腺癌2例,肾癌1例,来源不明3例.病灶累及单节段17例,两节段9例.23例伴不同程度的腰背部疼痛:神经功能按Frankel分级:B级6例,C级7例,D级11例,E级2例.术中采用骨水泥联合椎弓根螺钉重建脊柱稳定性,其中骨水泥填塞15个椎体,骨水泥前方重建9个椎体,骨水泥椎体成形11个椎体,10例合并骨质疏松患者同时采用骨水泥加强椎弓根钉道.结果:术中未发现骨水泥放热效应引起的神经功能受损.24例患者获得完整随访,随访时间3～42个月,平均18.2个月,23例术前有不同程度腰背疼痛者术后疼痛消失6例,缓解14例;术前伴神经功能障碍者17例(77%)获得神经功能改善.随访期间未发现骨水泥下沉、椎节塌陷及向前成角.1例骨水泥填塞术后3个月骨水泥界面出现松动,但未引起神经压迫症状.15例随访期间死亡.结论:在胸腰椎转移性肿瘤后路手术治疗中,根据患者的全身情况、预期寿命、肿瘤类型、转移椎体位置及骨密度,充分利用骨水泥独特的理化特性,进行多种不同方式的应用,可以减小手术创伤,提高生存质量.     

Favorable survival with combined treatment in a metastatic breast cancer patient undergoing hemodialysis: A case report

IntroductionManagement of breast cancer patients undergoing hemodialysis (HD) is difficult because of a lack of evidence about drug selection, dose adjustment, and surgical procedures. We herein present a case of metastatic breast cancer in a patient undergoing HD.Presentation of caseA 58-year-old Japanese woman with breast cancer undergoing HD underwent total mastectomy of the left breast and left axillary dissection. Histopathological examination revealed invasive ductal carcinoma, and the diagnosis was pT2N3cM0 Stage ⅢC. Immunostaining of the resected specimen indicated that the tumor was estrogen receptor-positive, progesterone receptor-negative, human epithelial growth factor receptor 2-positive, and the Ki-67 labeling index was 70%. A postoperative positron emission tomography/computed tomography (PET/CT) scan indicated fluorodeoxyglucose uptake in the supraclavicular nodes. She received adjuvant therapy of epirubicin and cyclophosphamide followed by docetaxel, trastuzumab (T-mab) and radiation therapy. However, she developed multiple liver metastases during adjuvant T-mab and hormone therapy. Therefore, her regimen was changed to trastuzumab emtansine (T-DM1) as first-line therapy, T-mab, pertuzumab (P-mab), and eribulin as second-line therapy, and T-mab, P-mab, and weekly paclitaxel as third-line therapy. Eventually, she was administered fourth-line treatment of T-mab, P-mab, and vinorelbine because of adverse events. She has survived more than 25 months after the initial detection of recurrence of breast cancer and maintained quality of life.ConclusionWe report a case of breast cancer in a patient undergoing HD. It is very difficult to identify the appropriate drugs and dosages in patients undergoing HD to improve survival and quality of life.     

Decrease of serum calcium concentration and lost influence of calcium on parathyroid hormone release in a patient with primary hyperparathyroidism after treatment with diphosphonates

Summary Prolonged decrease of elevated serum calcium levels after treatment with diphosphonates in patients with primary hyperparathyroidism (pHPT) is very rare. A patient with water clear cell hyperplasia and five enlarged glands is presented who received diphosphonates (day 1 through day 8 dichloromethylene diphosphonate orally and a single dose of 60 mg pamidronate on day 8 intravenously) leading to a significant fall in serum calcium levels. Surprisingly, there was no reactive increase in intact parathyroid hormone (PTH) in the following 18 days. Patients with missing PTH regulation to hypocalcemia after diphosphonates who need a period of stabilization prior to parathyroid surgery might benefit most from this therapy.     

Epithelioid hemangioma of bone: A unique case with multifocal metachronous bone lesions

Epithelioid hemangioma of bone is a rare vascular neoplasm with a ubiquitous distribution. To date, up to 25% epithelioid hemangioma of bone presents synchronous bone lesions. We report a unique case of epithelioid hemangioma with multifocal metachronous bone lesions without any fatal outcome observed after a long period. Importantly, a strong nuclear expression of FOSB antibody was detected by immunohistochemical analysis. In this case, the pathologic and radiologic findings are also described. We suggest that epithelioid hemangioma can present multifocal metachronous bone lesions without producing a fatal outcome.     

Treatment of Bone Metastases in Patients with Advanced Breast Cancer

Bone metastases are usually associated with a variety of skeletal related events (SREs), a term covering both complications (pathological fractures, spinal cord compression) and the need for therapeutic intervention (radiotherapy, surgery to bone) for painful bone lesions and/or lesions carrying a high risk of fracture by which the patient's quality of life, functioning, and independence may be compromised. In view of the availability of improved therapeutic approaches for oncological diseases and the resulting improvements of median overall survival, the aim of preventing and delaying the occurrence of SREs becomes more important. To avoid, wherever possible, therapies requiring hospitalization, is another relevant goal. In recent years, bisphosphonates, along with available tumor-specific medication (chemotherapy, hormone therapy), constituted the standard of care for preventing skeletal complications in treating patients with bone metastases. Recently, a therapeutical alternative with potentially superior efficacy has been found in denosumab, a fully human monoclonal antibody that binds to the receptor activator of nuclear factor-κB ligand (RANKL), thus preventing osteoclast-mediated bone resorption and specifically interfering with bone metabolism.