Dual modes of action of bisphosphonates on osteoclasts in vitro

Boonekamp, P.M.; Löwik, G.W.G.M.; Wee-Pals, Lianne J. A. van der; Lennep, M.L.L. van Wijk-van; Bijvoet, O.L.M.

doi:10.1016/8756-3282(85)90012-2

Cited by 84 publications

(105 citation statements)

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“…They are generally divided into N-containing (nitrogenous) bisphosphonates and non-N-containing bisphosphonates. In vivo, bisphosphonates have high affinity to hydroxyapatite on the bone surface and are delivered preferentially to mineral components of increased bone formation or resorption (Boonekamp et al, 1986). Nitrogenous bisphosphonates can inhibit the synthesis of farnesyl diphosphate in the cells, and decrease its downstream metabolite geranylgeranyl diphosphate.…”

Section: Discussionmentioning

confidence: 99%

Stimulation of Osteogenic Differentiation in Stromal Cells of Giant Cell Tumour of Bone by Zoledronic Acid

Yang¹,

Zheng²,

Li³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Therapeutic effects of zoledronic acid (ZOL) on giant cell tumour of bone (GCT) have been proven. Apoptosis induction was considered to be one of the mechanisms of ZOL tumour inhibition. In this study, we presented the possibility of an osteogenic differentiation stimulation mechanism of ZOL and further investigated dosage and time effects. We treated stromal cells of GCT (GCTSC) with ZOL for 48 hours at different concentrations (0 μM, 0.01 μM, 0.1 μM, 1 μM, 5 μM, 30 μM) and assessed apoptotic and osteogenic differentiation markers with immunohistochemical techniques and real-time quantitative RT-PCR. Our results suggested that ZOL enhanced mRNA expression of Cbfa-1, osterix and osteocalcin genes with a maximum effect at 1μM in GCTSC. Time course experiments indicated a time dependent osteogenic differentiation effect. In conclusion, ZOL may be considered as an adjuvant in the treatment of GCT not only by inducing apoptosis but also by stimulating osteogenic differentiation of remaining tumor stromal cells after surgery.

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Section: Discussionmentioning

confidence: 99%

Stimulation of Osteogenic Differentiation in Stromal Cells of Giant Cell Tumour of Bone by Zoledronic Acid

Yang¹,

Zheng²,

Li³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…21,22 Bisphosphonates are potent inhibitors of osteoclastic bone resorption and have effects on osteoclast recruitment, differentiation, activity, and apoptosis. [23][24][25][26] This study examined the effects of bisphosphonate treatment on stress fracture healing over an extended period. In contrast to complete fractures, stress fractures require early resorption during healing to enable new bone formation along the fracture line.…”

Section: Discussionmentioning

confidence: 99%

Bisphosphonate treatment delays stress fracture remodeling in the rat ulna

Kidd

Cowling

et al. 2011

Journal Orthopaedic Research

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Because bisphosphonates (BPs) are potent inhibitors of bone resorption, we hypothesized that they would retard direct remodeling of stress fractures. The aim of this study was to determine the effect of risedronate on direct remodeling and woven bone callus formation following stress fracture formation in the rat ulna. In 135 adult female Wistar rats, cyclic loading of the ulna created stress fractures. Rats were treated daily with oral saline, or risedronate at 0.1 or 1.0 mg/kg. From each bone, histomorphometry was performed on sections stained with toluidine blue at a standard level along the fracture. The high dose of risedronate caused a significant decrease in the percentage of repaired stress fracture and bone resorption along the stress fracture line at 6 and 10 weeks after loading (p < 0.05). At this dose, intracortical resorption was significantly reduced at 10 weeks after loading and intracortical new bone area was significantly reduced at 6 and 10 weeks. Woven bone formation and consolidation phases of stress fracture repair were not affected by low or high doses of risedronate. In conclusion, high dose bisphosphonate treatment impaired healing of a large stress fracture line by reducing the volume of bone resorbed and replaced during remodeling. We also confirmed that periosteal callus formation was not adversely affected by risedronate treatment. ß

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“…In vivo, bisphosphonates bind strongly to hydroxyapatite on the bone surface and are preferentially delivered to sites of increased bone formation or resorption. They are potent inhibitors of osteoclast-mediated bone resorption (Boonecamp et al, 1986) and are effective in lowering serum calcium concentrations in patients with hypercalcaemia of malignancy (Ryzen et al, 1985;Kanis et al, 1987). Bisphosphonates are also used in the treatment of Paget's disease of bone (Altman et al, 1973;Plasmans et al, 1978) and bone lesions associated with multiple myeloma (Berenson et al, 1996).…”

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confidence: 99%

“…Bisphosphonates are also used in the treatment of Paget's disease of bone (Altman et al, 1973;Plasmans et al, 1978) and bone lesions associated with multiple myeloma (Berenson et al, 1996). The mechanisms by which bisphosphonates inhibit osteoclast-mediated bone resorption remain to be determined, but may involve inhibition of formation of osteoclasts from immature precursor cells (Boonecamp et al, 1986;Lowik et al, 1988;Hughes et al, 1989) and/or direct inhibition of resorption via induction of apoptosis in mature osteoclasts (Lowik et al, 1988;Hughes et al, 1995;Selander et al, 1996). More recently, several reports have indicated that bisphosphonates have direct effects on other cell types which may have important implications in the treatment of patients with cancer-induced bone disease.…”

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confidence: 99%

Bisphosphonates induce apoptosis in human breast cancer cell lines

et al. 2000

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Over 80% of women with advanced breast cancer ultimately develop bone metastases which account significantly for morbidity and mortality. Breast cancer metastases in bone can cause intractable pain, bone fracture, spinal cord compression and hypercalcaemia. It also signifies that the malignant process is incurable since, once tumour cells become lodged in the skeleton, therapy can only be given with palliative intent. This includes analgesics, radiation therapy and systemic treatments such as hormone or chemotherapy. The events leading to the development of bone lesions in patients with carcinoma of the breast are poorly understood. However, histomorphometric studies have shown that tumour cells are adjacent to actively resorbing osteoclasts (Boyde et al, 1986) and it has been suggested that breast carcinoma cells possess the capacity to recruit and stimulate osteoclasts by producing stimulatory factors (Boyde et al, 1986). Parathyroid hormone related peptide (PTHrP) is thought to be a major candidate factor produced by breast cancer cells which may promote osteoclastic activity at metastatic sites in bone (Powell et al, 1991).Bisphosphonates (BPs) are analogues of endogenous pyrophosphates in which a carbon atom replaces the central atom of oxygen. In vivo, bisphosphonates bind strongly to hydroxyapatite on the bone surface and are preferentially delivered to sites of increased bone formation or resorption. They are potent inhibitors of osteoclast-mediated bone resorption (Boonecamp et al, 1986) and are effective in lowering serum calcium concentrations in patients with hypercalcaemia of malignancy (Ryzen et al, 1985;Kanis et al, 1987). Bisphosphonates are also used in the treatment of Paget's disease of bone (Altman et al, 1973;Plasmans et al, 1978) and bone lesions associated with multiple myeloma (Berenson et al, 1996). The mechanisms by which bisphosphonates inhibit osteoclast-mediated bone resorption remain to be determined, but may involve inhibition of formation of osteoclasts from immature precursor cells (Boonecamp et al, 1986;Lowik et al, 1988;Hughes et al, 1989) and/or direct inhibition of resorption via induction of apoptosis in mature osteoclasts (Lowik et al, 1988;Hughes et al, 1995;Selander et al, 1996). More recently, several reports have indicated that bisphosphonates have direct effects on other cell types which may have important implications in the treatment of patients with cancer-induced bone disease. Treatment with intravenous pamidronate (Hortobagyi et al, 1998) and oral clodronate (Paterson et al, 1993) have been reported to reduce the frequency of skeletal complications in established bone disease. Oral clodronate has also been shown to decrease the frequency of skeletal metastases in women who had recurrent breast cancer but without bony involvement (Kanis et al, 1996). Moreover, oral clodronate has recently been shown to increase survival in women with breast cancer, when given at the time of initial diagnosis to patients who have bone marrow micrometastases at the time of surgery fo...

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Dual modes of action of bisphosphonates on osteoclasts in vitro

Cited by 84 publications

References 0 publications

Stimulation of Osteogenic Differentiation in Stromal Cells of Giant Cell Tumour of Bone by Zoledronic Acid

Stimulation of Osteogenic Differentiation in Stromal Cells of Giant Cell Tumour of Bone by Zoledronic Acid

Bisphosphonate treatment delays stress fracture remodeling in the rat ulna

Bisphosphonates induce apoptosis in human breast cancer cell lines

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