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

Abstract

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...

Microgravity-Related Changes in Bone Density and Treatment Options: A Systematic Review

“…Furthermore, 3-month-old male Wistar rats subjected to right hindlimb immobilization for 10 weeks to induce osteopenia were treated with zoledronic acid and alfacalcidol. This combination therapy was more effective than each drug administered as a monotherapy for the treatment of disuse osteoporosis [ 74 ]. However, SERM and teriparatide did not reveal any effect on BL [ 65 ], while BP, SERM, anti-RANKL, and teriparatide demonstrated a significant increase in BMD in MP women [ 99 , 100 , 101 , 102 , 103 , 104 ].…”

Role of acid sphingomyelinase in the age-dependent dysregulation of sphingolipids turnover in the tissues of rats

“…hand, in rats, chronic imipramine treatment can inhibit body weight gain (Okiyama et al 1986). At the same time, zoledronic acid chronic administration has been reported not to influence on body weight gain in rats, but in humans it can lead to either weight increase or weight loss (Khajuria et al 2015). Our previous works showed that optimal administration period for imipramine to inhibit effectively ASMase activity in 24-month old rats was 14 days (Garkavenko et al 2012).…”

Can Alfacalcidol ameliorate Atorvastatin-induced myopathy in adult male rats? A histological study

“…Each rat received 0.5 ml distilled water containing 2 mg Ator. Group ΙII (Ator and ALF treated group): Rats of this group received Ator as in group ΙΙ concomitantly with Alfacalcidol (0.5µg/ kg/day) [12] for 4 weeks [19] . Each rat received daily 0.5 ml distilled water containing 0.1 µg ALF.…”

“…Many patients cannot obtain the lower level of cholesterol at low doses of Statins, subsequently they use higher doses, thus the risk of myopathy is elevated [11] . Alfacalcidol (ALF), 1 α hydroxyl vitamin D 3, is a synthetic vitamin D analog regulating the calcium, and is frequently utilized to treat osteoporosis [12] . Additionally, it has a unique pattern of pleiotropic effects on, e.g.…”