Osteosclerotic Bone Metastases Research Articles

Sphenoid wing Metastasis from Occult Prostatic Carcinoma

Prostatic carcinoma commonly metastasizes to skeletal bone or vertebral bodies, forming osteosclerotic bone metastases, also it metastasizes to the head and neck region. This is the case of prostatic carcinoma presenting with an osteosclerotic metastasis to the sphenoid wing. A 64-year-old man complained of progressive left visual loss and exophthalmos. Computed tomography (CT) revealed a clear soft-density mass in the left sphenoid wing and fluorodeoxyglucose-positron emission tomography (FDG-PET) showed almost no uptake of FDG in this lesion. Biopsy from the sphenoid wing was obtained with the canine fossa approach. Pathological diagnosis was prostate adenocarcinoma. This case serves as a reminder that prostate carcinoma should be considered whenever osteosclerotic bone changes are observed on CT. FDGPET proved to be less sensitive than scintigraphy for the diagnosis of osteosclerotic metastasis from prostate carcinoma.

Usefulness of (18)F-fluoride PET/CT in Breast Cancer Patients with Osteosclerotic Bone Metastases.

Bone metastasis is an important factor for the treatment and prognosis of breast cancer patients. Whole-body bone scintigraphy (WBBS) can evaluate skeletal metastases, and (18)F-FDG PET/CT seems to exhibit high specificity and accuracy in detecting bone metastases. However, there is a limitation of (18)F-FDG PET in assessing sclerotic bone metastases because some lesions may be undetectable. Recent studies showed that (18)F-fluoride PET/CT is more sensitive than WBBS in detecting bone metastases. This study aims to evaluate the usefulness of (18)F-fluoride PET/CT by comparing it with WBBS and (18)F-FDG PET/CT in breast cancer patients with osteosclerotic skeletal metastases. Nine breast cancer patients with suspected bone metastases (9 females; mean age ± SD, 55.6 ± 10.0 years) underwent (99m)Tc-MDP WBBS, (18)F-FDG PET/CT and (18)F-fluoride PET/CT. Lesion-based analysis of five regions of the skeletons (skull, vertebral column, thoracic cage, pelvic bones and long bones of extremities) and patient-based analysis were performed. (18)F-fluoride PET/CT, (18)F-FDG PET/CT and WBBS detected 49, 20 and 25 true metastases, respectively. Sensitivity, specificity, positive predictive value and negative predictive value of (18)F-fluoride PET/CT were 94.2%, 46.3%, 57.7% and 91.2%, respectively. Most true metastatic lesions on (18)F-fluoride PET/CT had osteosclerotic change (45/49, 91.8%), and only four lesions showed osteolytic change. Most lesions on (18)F-FDG PET/CT also demonstrated osteosclerotic change (17/20, 85.0%) with three osteolytic lesions. All true metastatic lesions detected on WBBS and (18)F-FDG PET/CT were identified on (18)F-fluoride PET/CT. (18)F-fluoride PET/CT is superior to WBBS or (18)F-FDG PET/CT in detecting osteosclerotic metastatic lesions. (18)F-fluoride PET/CT might be useful in evaluating osteosclerotic metastases in breast cancer patients.

早期胃癌術後１０年以上の経過で造骨性骨転移を発症し診断に苦慮した維持透析患者の１例

早期胃癌術後10年以上の経過で造骨性骨転移を発症し診断に苦慮した維持透析患者の1例を経験したので報告する．症例は1992年から維持透析中の60歳，男性．1993年，早期胃癌にて胃全摘術が施行された．2003年頃より血中ALPの高値を認めたため，2004年骨生検を施行したところ，著明な骨硬化像と，腺癌の骨転移所見を認めた．全身検索が施行されたが原発巣の特定には至らなかった．2005年9月便通異常，腹痛を主訴に入院し，大腸鏡にて転移性直腸癌と診断された．多発性骨転移，腹膜播種の所見もあり根治療法の適応なく，全身衰弱のため12月永眠した．剖検の結果，全身に低分化型腺癌の転移所見が認められ，腺癌の組織学的所見は胃癌に矛盾しなかった．経過としては非典型的だったが，10年以上の経過での胃癌の全身転移と診断された．維持透析患者に造骨性変化を認めた場合，鑑別疾患として腎性骨異栄養症だけでなく骨転移の可能性も考慮する必要がある．

Lack of Noggin Expression by Cancer Cells Is a Determinant of the Osteoblast Response in Bone Metastases

Prostate and mammary cancer bone metastases can be osteoblastic or osteolytic, but the mechanisms determining these features are unclear. Bone morphogenetic and Wnt proteins are osteoinductive molecules. Their activity is modulated by antagonists such as noggin and dickkopf-1. Differential expression analysis of bone morphogenetic and Wnt protein antagonists in human prostate and mammary cancer cell lines showed that osteolytic cell lines constitutively express in vitro noggin and dickkopf-1 and at least one of the osteolytic cytokines parathyroid hormone-related protein, colony-stimulating factor-1, and interleukin-8. In contrast, osteoinductive cell lines express neither noggin nor dickkopf-1 nor osteolytic cytokines in vitro. The noggin differential expression profile observed in vitro was confirmed in vivo in prostate cancer cell lines xenografted into bone and in clinical samples of bone metastasis. Forced noggin expression in an osteoinductive prostate cancer cell line abolished the osteoblast response induced in vivo by its intraosseous xenografts. Basal bone resorption and tumor growth kinetics were marginally affected. Lack of noggin and possibly dickkopf-1 expression by cancer cells may be a relevant mechanism contributing to the osteoblast response in bone metastases. Concomitant lack of osteolytic cytokines may be permissive of this effect. Noggin is a candidate drug for the adjuvant therapy of bone metastasis.

Type I collagen degradation product (ICTP) gives information about the nature of bone metastases and has prognostic value in prostate cancer.

Although osteosclerotic bone metastases are characteristic of prostate cancer, mixed metastases with a lytic component are not uncommon. Type I collagen is synthesised by osteoblasts and accounts for about 90% of the organic matrix of bone. We have used new specific immunoassays for PICP (carboxy-terminal propeptide of type I procollagen) and ICTP (cross-linked carboxy-terminal telopeptide of type I collagen) which allow simultaneous assessment of the synthesis and degradation of type I collagen respectively. Forty patients with bone metastases due to prostate cancer at the time of diagnosis were investigated with these methods. Twenty-three of them had sclerotic (S) and 17 had mixed metastases with sclerotic and lytic components (S + L) as assessed by radiographs. The concentrations of PICP and ICTP in serum as well as the activity of alkaline phosphatase (AP) were increased in all patients of the S + L group, who had more aggressive bone disease and a shorter survival than the S group (P < 0.017). The ICTP level was above the reference range in half of the patients in the S group, whereas the PICP and AP levels were elevated in 35%. Of the bone markers, only ICTP was of prognostic significance (P < .05). We conclude that ICTP and PICP give information about the type and activity of the skeletal metastases. In addition, ICTP predicts prognosis.

Hypercalcaemia of malignancy.

Hypercalcaemia in malignancy is a major clinical problem. It contributes significantly to morbidity and mortality and can present difficult diagnostic and management dilemmas. Direct bony invasion by tumour cells rather than humorally mediated hypercalcaemia is probably the most common cause of malignant hypercalcaemia. Yet even in this situation the mechanism of bone resorption or the reason that the normal homeostatic mechanisms cannot cope with the calcium load are poorly understood. It is likely that the humoral and paracrine factors produced by tumours which result in hypercalcaemia or in osteosclerotic bone metastases, are interposing themselves into the normal regulatory processes and deranging them. Humoral hypercalcaemia of malignancy is an important model for studying these questions, and it also provides some insight into the normal regulation of bone turnover. This review will examine the animal models and human syndromes of malignant hypercalcaemia and show how animal models, although helpful, fail to delineate the relative importance of the various potential humoral factors. A most interesting recent development in this area is the description of a new hormone, the parathyroid hormone-related peptide, which may explain many of the cases of humoral hypercalcaemia of malignancy. It is also a useful model with multiple sites of action within the bone and calcium homeostatic process. The active hormonal form of vitamin D3, 1,25-dihydroxyvitamin D3, may also be involved in a small proportion of cases, but again it is a useful model of some of the factors that may operate. Of considerable interest are the tumour derived factors, such as the transforming growth factors, and the cytokines, such as tumour necrosis factors, interleukins, and haemopoietic colony stimulating factors. Prostanoids are seldom of major importance, but may be important in certain tumour types. Osteosclerotic metastases, although seldom associated with hypercalcaemia, may provide insight into osteoblast regulating factors. Treatment of hypercalcaemia is discussed to show ways in which response to treatment may shed light on underlying pathophysiological mechanisms. Most effective treatments have many potential modes of action, and further study of the interactions of these agents and tumour types may help to unravel some of the enigmas in this human syndrome. The major advances in this complex problem involve the realisation of the necessity of multiple sites of action, including renal calcium handling as well as relative increases in bone resorption and/or intestinal calcium absorption.(ABSTRACT TRUNCATED AT 400 WORDS)

The presence of tumor cells in bone marrow at the time of first recurrence of breast cancer.

The occurrence of bone marrow carcinosis was investigated in 380 patients at the time of first recurrence of breast cancer. Results were related to results from radiographic bone survey, 99mTc MDP bone scintigraphy, clinical examination and serum alkaline phosphatase and serum calcium levels. Eighty-seven patients (23%) had tumor cells in the bone marrow. X-rays showed metastases in 78% of the patients with and in 16% of the patients without bone marrow carcinosis. The diagnostic efficiency of x-rays with bone marrow biopsy as the key diagnostic factor was 83%, and it was superior to that of other investigation methods. Bone tissue biopsies were positive alone in 15 patients (17%) and marrow aspirations were positive alone in seven patients (8%). Imprint preparations were positive alone in 7% of the patients and bone tissue biopsy in 5% of the patients. Heavy tumor infiltration (greater than or equal to 50%) of the bone marrow was associated with the occurrence of numerous regions of radiographically involved bone lesions and with histopathologic evidence of bone destruction. Furthermore, pronounced bone formation and marrow fibrosis were more commonly seen in patients with osteosclerotic bone metastases than in patients with osteolytic bone metastases. This study provides evidence that the primary soil of metastatic bone disease in human breast cancer is the bone marrow and that radiographic evidence of bone metastases is a result of an invasion and destruction of the bone tissue matrix by tumor cells from the marrow cavity.

Increased serum calcitonin in patients with mammary carcinoma.

Serum calcitonin war within normal range in 11 patients with benign breast tumour. In cases with local malignant breast tumour increased calcitonin was found in 25 per cent (4/16), in cases with regional metastases in 40 per cent (2/5), and in cases with osteolytic bone metastases in 77 per cent (10/13). Two patients with osteosclerotic bone metastases had low calcitonin concentration. It is suggested that increased calcitonin in mammary carcinoma is a physiologic response to osteolytic bone metastases.