Additive effect of PTH (1–34) and zoledronate in the prevention of disuse osteopenia in rats

Vegger, Jens Bay; Nielsen, Esben; Brüel, Annemarie; Thomsen, Jesper Skovhus

doi:10.1016/j.bone.2014.06.020

Cited by 31 publications

(24 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…27,28 We then treated SCD and control mice with Zol (100 mg/kg IP, single dose) 23 to investigate whether it might effectively counteract bone impairment of SCD mice.…”

Section: Zoledronic Acid Prevents Bone Loss and Ameliorates Osteogenimentioning

confidence: 99%

“…Whenever indicated, Zol was administrated at a dosage of 100 mg/kg intraperitoneally (IP) based on previous reports. 23,24 Flow cytometric analysis of mouse erythroid precursors of murine bone marrow erythroblasts Flow cytometric analysis of erythroid precursors from bone marrow and spleen of mice from the 4 strains was carried out as previously described using the CD44-TER-119 strategy. 25,26 Measurements of bone homeostasis and turnover For details of bone histomorphometry and bone turnover, see supplemental Methods, available on the Blood Web site.…”

Section: Mouse Model and Study Designmentioning

confidence: 99%

See 1 more Smart Citation

Hypoxia-reperfusion affects osteogenic lineage and promotes sickle cell bone disease

Carbonare

Mattè

Valenti

et al. 2015

Blood

View full text Add to dashboard Cite

Key Points• In SCD, recurrent vasoocclusive crisis suppresses osteogenic lineage and activates osteoclasts.• Zoledronic acid acting on both osteoclast and osteoblast compartments is a multimodal therapy to prevent SBD.Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder, characterized by severe organ complication. Sickle bone disease (SBD) affects a large part of the SCD patient population, and its pathogenesis has been only partially investigated. Here, we studied bone homeostasis in a humanized mouse model for SCD. Under normoxia, SCD mice display bone loss and bone impairment, with increased osteoclast and reduced osteoblast activity. Hypoxia/reperfusion (H/R) stress, mimicking acute vaso-occlusive crises (VOCs), increased bone turnover, osteoclast activity (RankL), and osteoclast recruitment (Rank) with upregulation of IL-6 as proresorptive cytokine. This was associated with further suppression of osteogenic lineage (Runx2, Sparc). To interfere with the development of SBD, zoledronic acid (Zol), a potent inhibitor of osteoclast activity/ osteoclastogenesis and promoter of osteogenic lineage, was used in H/R-exposed mice. Zol markedly inhibited osteoclast activity and recruitment, promoting osteogenic lineage. The recurrent H/R stress further worsened bone structure, increased bone turnover, depressed osteoblastogenesis (Runx2, Sparc), and increased both osteoclast activity (RankL, Cathepsin k) and osteoclast recruitment (Rank) in SCD mice compared with either normoxic or single-H/R-episode SCD mice. Zol used before recurrent VOCs prevented bone impairment and promoted osteogenic lineage. Our findings support the view that SBD is related to osteoblast impairment, and increased osteoclast activity resulted from local hypoxia, oxidative stress, and the release of proresorptive cytokine such as IL-6. Zol might act on both the osteoclast and osteoblast compartments as multimodal therapy to prevent SBD. (Blood. 2015;126(20):2320-2328 IntroductionSickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder, which affects approximately 75 000 individuals in the United States and almost 20 000 to 25 000 individuals in Europe, this latter mainly related to the immigration fluxes from endemic areas such as Sub-Saharan Africa to European countries.1-3 Studies of the global burden of disease have pointed out the invalidating impact of SCD on patient quality of life.2 This requires the development of new therapeutic options to treat sickle cell-related acute and chronic complications.SCD is caused by a point mutation in the b-globin gene resulting in the synthesis of pathologic hemoglobin S (HbS). HbS displays peculiar biochemical characteristics, polymerizing when deoxygenated with associated reduction in cell ion and water content (cell dehydration), increased red cell density, and further acceleration of HbS polymerization. [4][5][6] Pathophysiologic studies have shown that dense, dehydrated red cells play a central role in acute and chronic clinical manifestations of ...

show abstract

“…27,28 We then treated SCD and control mice with Zol (100 mg/kg IP, single dose) 23 to investigate whether it might effectively counteract bone impairment of SCD mice.…”

Section: Zoledronic Acid Prevents Bone Loss and Ameliorates Osteogenimentioning

confidence: 99%

Section: Mouse Model and Study Designmentioning

confidence: 99%

Hypoxia-reperfusion affects osteogenic lineage and promotes sickle cell bone disease

Carbonare

Mattè

Valenti

et al. 2015

Blood

View full text Add to dashboard Cite

show abstract

“…which prevent further bone loss in established osteoporosis but do not change the bone mass or replenish the already lost bone. 7,10,25 In the present experimental research we preferred ZOL over other bisphosphonates available in India. ZOL has several advantages over other bisphosphonates: (1) the obvious advantage of ZOL over other bisphosphonates is the high level of adherence that is possible under the controlled environment of a once yearly infusion administered under medical supervision.…”

Section: Discussionmentioning

confidence: 98%

“…[5][6][7][8] The effect of a single treatment of ZOL for immobilization-induced osteoporosis has been shown in animal studies. 9,10 Although anti-resorptive agents such as bisphosphonates are effective in reducing bone loss, they are not able to induce formation of a new bone. 7,10 Alfacalcidol (1 alpha-hydroxy Vitamin D 3 -ALF) is a synthetic Vitamin D analog, a calcium regulating hormone, and is frequently used in several countries to treat osteoporosis.…”

Section: Introductionmentioning

confidence: 99%

“…9,10 Although anti-resorptive agents such as bisphosphonates are effective in reducing bone loss, they are not able to induce formation of a new bone. 7,10 Alfacalcidol (1 alpha-hydroxy Vitamin D 3 -ALF) is a synthetic Vitamin D analog, a calcium regulating hormone, and is frequently used in several countries to treat osteoporosis. 9,11 ALF reduces parathyroid hormone levels, as a result of both increased calcium absorption and an inhibition of the proliferation of the parathyroid gland, and also decreases the release of pro-inflammatory cytokines, which contribute to osteoclast activation.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Additive effect of zoledronic acid and alfacalcidol in the treatment of disuse osteoporosis in rats

Khajuria

Disha

Razdan

et al. 2015

Revista Brasileira de Reumatologia (English Edition)

View full text Add to dashboard Cite

r e v b r a s r e u m a t o l . 2 0 1 5;5 5(3):240-250 w w w . r e u m a t o l o g i a . c o m . b r a b s t r a c tObjectives: Disuse by bed rest, limb immobilization or space flight causes rapid bone loss. We conducted the present study to investigate the therapeutic effects of zoledronic acid (ZOL), alone and in combination with alfacalcidol (ALF) in a rat model of disuse osteoporosis.Methods: In the present study, 3-month-old male Wistar rats had their right hind-limb immobilized (RHLI) for 10 weeks to induce osteopenia, then were divided into four groups: 1 -RHLI positive control; 2 -RHLI plus ZOL (50 g/kg, i.v. single dose); 3 -RHLI plus ALF (0.5 g/kg, oral gauge daily); 4 -RHLI plus ALF (0.5 g/kg, oral gauge daily) plus ZOL (50 g/kg, i.v. single dose) for another 10 weeks. One group of non-immobilized rats was used as negative control. At the end of the treatment, the femurs were removed and tested for bone porosity, bone mechanical properties, and bone dry and ash weight.Results: Combination therapy with ZOL plus ALF was more effective in decreasing bone porosity than each drug administered as monotherapy in RHLI rats. With respect to improvement in the mechanical strength of the femoral mid-shaft, the combination treatment of ZOL plus ALF was more effective than each drug administered as a monotherapy. Moreover, combination therapy using ZOL plus ALF was more effective in improving dry bone and ash weight, than single-drug therapy using ZOL or ALF in RHLI rats.Conclusions: These data suggest that combination therapy with ZOL plus ALF represents a potentially useful therapeutic option for the treatment of disuse osteoporosis. r e v b r a s r e u m a t o l . 2 0 1 5;5 5(3):240-250 241 Efeito combinado do ácido zoledrônico e do alfacalcidol no tratamento da osteoporose por desuso em ratos Palavras-chave: Osteoporose por desuso Estudo com ratos Ácido zoledrônico Alfacalcidol r e s u m o Objetivos: O desuso pelo repouso no leito, pela imobilização de membros ou por missões espaciais provoca a perda óssea rápida. Fez-se este estudo para investigar os efeitos terapêuticos do ácido zoledrônico (ZOL), isoladamente e em combinação ao alfacalcidol (ALF), em um modelo de rato com osteoporose por desuso.Métodos: Ratos Wistar machos de três meses foram submetidos à imobilização da pata traseira direita (IPTD) por 10 semanas para induzir a osteopenia; em seguida, foram divididos em quatro grupos: 1 -IPTD para controle positivo; 2 -IPTD mais ZOL (50 g/kg, dose única intravenosa); 3 -IPTD mais ALF (0,5 g/kg, via oral diariamente); 4 -IPTD mais ALF (0,5 g/kg, via oral diariamente) mais ZOL (50 g/kg, dose única intravenosa) por outras 10 semanas. Um grupo de ratos não imobilizados foi usado como controle negativo. No fim do tratamento, os fêmures foram removidos e testaram-se a porosidade do osso e suas propriedades mecânicas, além do peso seco e das cinzas do osso.Resultados: A terapia combinada com ZOL mais ALF foi mais eficaz em reduzir a porosidade do osso do que a monoterapia com um dos fármacos administrado isoladame...

show abstract

Effects of combined teriparatide and zoledronic acid on posterior lumbar vertebral fusion in an aged ovariectomized rat model of osteopenia

Yishake

Yasen

Jiang

et al. 2018

Journal Orthopaedic Research

View full text Add to dashboard Cite

There has been no study regarding the effect of a combination of teriparatide (TPTD) and zoledronic acid (ZA) on vertebral fusion. In this study, we investigate the effect of single and combined TPTD and ZA treatment on lumbar vertebral fusion in aged ovariectomized (OVX) rats. Sixty two-month-old female Sprague-Dawley rats were ovariectomized and underwent bilateral L4-L5 posterolateral intertransverse fusion after 10 months. The OVX rats received vehicle (control) treatment, or ZA (100 µg/kg, once), or TPTD (60 µg/kg/2 d for 42 d), or ZA + TPTD until they were euthanized at 6 weeks following lumbar vertebral fusion. The lumbar spine was harvested. Bone mineral density (BMD), bone fusion, bone volume (BV), and bone formation rate (BFR)were analyzed by dual-energy X-ray absorptiometry (DXA), radiography, micro-computed tomography, and histomorphometry. Compared with vehicle (control) treatment, ZA and TPTD monotherapy increased bone volume (BV) at fusion site, and ZA + TPTD combined therapy had an additive effect. Treatment with TPTD and ZA + TPTD increased the bone fusion rate when compared with the control group. ZA monotherapy did not alter the rate of bone fusion. The TPTD and ZA + TPTD treatment groups had increased mineral apposition rate (MAR), mineralizing surfaces/bone surface ((MS/BS), and BFR/BS compared with the OVX group. Our experiment confirm that the monotherapy with TPTD and combination therapy with ZA + TPTD in an OVX rat model of osteopenia following lumbar vertebral fusion surgery increased bone fusion mass and bone fusion rate, and ZA + TPTD combined therapy had an additive effect on bone fusion mass. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:937-944, 2018.

show abstract

Additive effect of PTH (1–34) and zoledronate in the prevention of disuse osteopenia in rats

Cited by 31 publications

References 54 publications

Hypoxia-reperfusion affects osteogenic lineage and promotes sickle cell bone disease

Hypoxia-reperfusion affects osteogenic lineage and promotes sickle cell bone disease

Additive effect of zoledronic acid and alfacalcidol in the treatment of disuse osteoporosis in rats

Effects of combined teriparatide and zoledronic acid on posterior lumbar vertebral fusion in an aged ovariectomized rat model of osteopenia

Contact Info

Product

Resources

About