Osteoclast inhibition by pamidronate in metastatic prostate cancer: a preliminary study

Clarke, Noel W.; Holbrook, Ian; McClure, John; George, N. J. R.

doi:10.1038/bjc.1991.97

Cited by 67 publications

(18 citation statements)

References 12 publications

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“…The bisphosphonates are expensive drugs and, although confirmatory studies are needed, our data suggest that the most cost-efficient use of bisphosphonates is to lmit repeated treatment to those who have shown a clear subjective response to the first treatment. The ability to be able to achieve symptomatic response in sclerotic metastatic bone disease through selective inhibition of bone resorption is an important clinical observation and confirms previous small studies with pamidronate (Clarke et al, 1991) and clodronate (Adami & Mian, 1989) (Galasko, 1976;Colman, 1991). The sclerotic radiographic appearances mask the uncoupling and imbalance of bone remodelling that occurs in many patients with bone metastases, with the excessive new bone formation occurring away from sites of osteoclastic bone resorption.…”

Section: Disasssionsupporting

confidence: 57%

High-dose intravenous pamidronate for metastatic bone pain

Purohit

Anthony²,

Radstone³

et al. 1994

Br J Cancer

139

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Section: Disasssionsupporting

confidence: 57%

High-dose intravenous pamidronate for metastatic bone pain

Purohit

Anthony²,

Radstone³

et al. 1994

Br J Cancer

139

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“…Myeloma, breast and prostate cancer are seen frequently in the elderly and can cause bone lesions ranging from 65 to 100% [30, 31, 32, 33]; a change in the frequency of SRE (fracture, spinal cord compression, pain) should be associated with an improvement in quality of life [34]. Osteolytic bone resorption is a key element in bone metabolism.…”

Section: Discussionmentioning

confidence: 99%

Safety of Long-Term Administration of Bisphosphonates in Elderly Cancer Patients

et al. 2004

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Background: To evaluate the effectiveness and tolerability of the long-term treatment bone metastases with pamidronate in older patients. Materials and Methods: Twenty-two ambulatory patients aged 70 or older were included in the study. The median age was 73 (range 70–77). Ten patients (46%) were affected by breast carcinoma, 7 (32%) by prostate carcinoma and 5 (22%) by multiple myeloma. Nine (40%) patients presented co-morbidity. All of the patients presented at least one metastatic lytic bone lesion measuring 1 cm or more in diameter; the median lesion number was 2 (range 1–4). Hormonal therapy or chemotherapy regimen, were allowed as clinically required. Patients were treated with a fixed dose of sodium pamidronate, 90 mg in 3 h infusion every 4 weeks. Results: Partial response was shown in 6 (28%) patients, stable disease in 11 (50%), and progression (PD) in 5 (22%). 2 out of 5 patients with PD presented skeletal-related events (SREs) such as bone fracture. The median treatment duration was 19 months. The treatment was well tolerated; in 5 patients (23%) a GI fever was observed, in 3 patients (18%) G1 nausea, and in 3 patients (14) G1 diarrhea. Two cases (9%) of acute renal insufficiency (creatinine 1.7 and 1.6 mg/dl), and 3 cases (14%) of hypocalcemia (7.6, 7.5 and 7.8 mg/dl) were also registered. The renal dysfunction was reversible and without consequence. Conclusion: Our experience suggests that the bisphosphonates long-term administration is useful and did not cause significant side effects in elderly subjects. Low-grade pyrexia, nausea/vomiting, acute/reversible renal dysfunction and hypo-calcemia were the most frequent side effects reported. However, they were of low grade and in most cases, did not require dose modifications and/or hospitalization.

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“…In 1983 the bisphosphonate clodronate was shown to reduce hypercalcemia, bone pain, and osteolytic progression in breast cancer patients with bone metastases (306). In 1991, pamidronate was shown to reduce bone destruction in breast cancer patients with bone metastases and in myeloma patients (307) and prostate cancer patients with bone metastases (308). Ten years later, zoledronic acid (ZOL) was shown to reduce SREs in patients with bone metastases (309).…”

Section: G Rankl and Rankl Inhibition In Bone Metastasis And Multiplmentioning

confidence: 99%

Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease

2007

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Osteoclasts and osteoblasts dictate skeletal mass, structure, and strength via their respective roles in resorbing and forming bone. Bone remodeling is a spatially coordinated lifelong process whereby old bone is removed by osteoclasts and replaced by bone-forming osteoblasts. The refilling of resorption cavities is incomplete in many pathological states, which leads to a net loss of bone mass with each remodeling cycle. Postmenopausal osteoporosis and other conditions are associated with an increased rate of bone remodeling, which leads to accelerated bone loss and increased risk of fracture. Bone resorption is dependent on a cytokine known as RANKL (receptor activator of nuclear factor B ligand), a TNF family member that is essential for osteoclast formation, activity, and survival in normal and pathological states of bone remodeling. The catabolic effects of RANKL are prevented by osteoprotegerin (OPG), a TNF receptor family member that binds RANKL and thereby prevents activation of its single cognate receptor called RANK. Osteoclast activity is likely to depend, at least in part, on the relative balance of RANKL and OPG. Studies in numerous animal models of bone disease show that RANKL inhibition leads to marked suppression of bone resorption and increases in cortical and cancellous bone volume, density, and strength. RANKL inhibitors also prevent focal bone loss that occurs in animal models of rheumatoid arthritis and bone metastasis. Clinical trials are exploring the effects of denosumab, a fully human anti-RANKL antibody, on bone loss in patients with osteoporosis, bone metastasis, myeloma, and rheumatoid arthritis. (Endocrine Reviews 29: 2008)

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Osteoclast inhibition by pamidronate in metastatic prostate cancer: a preliminary study

Cited by 67 publications

References 12 publications

High-dose intravenous pamidronate for metastatic bone pain

High-dose intravenous pamidronate for metastatic bone pain

Safety of Long-Term Administration of Bisphosphonates in Elderly Cancer Patients

Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease

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