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Zoledronic acid in combination with alfacalcidol has additive effects on trabecular microarchitecture and mechanical properties in osteopenic ovariectomized rats

  • Original Article
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Journal of Orthopaedic Science

Abstract

Background

We conducted the present study to investigate the therapeutic effects of the antiresorptive agent zoledronic acid (ZOL), alone and in combination with alfacalcidol (ALF), in a rat model of postmenopausal osteoporosis.

Methods

Female Wistar rats were ovariectomized (OVX) or sham-operated at 3 months of age. Twelve weeks post surgery, rats were randomized into six groups: (1) sham + vehicle, (2) OVX + vehicle, (3) OVX + ZOL (100 μg/kg, i.v. single dose), (4) OVX + ZOL (50 μg/kg, i.v. single dose), (5) OVX + ALF (0.5 μg/kg, oral gauge daily) and (6) OVX + ZOL (50 μg/kg, i.v. single dose) + ALF (0.5 μg/kg, oral gauge daily) for 12 weeks. After treatment, we evaluated the mechanical properties of the lumbar vertebra and femoral mid-shaft. Femurs were also tested for bone density, porosity and trabecular micro-architecture. Biochemical markers in serum and urine were also determined.

Results

With respect to improvement in the mechanical strength of the lumbar spine and the femoral mid-shaft, the combination treatment of ZOL and ALF was more effective than each administered as a monotherapy. Moreover, combination therapy using ZOL and ALF preserved the trabecular micro-architecture and cortical bone porosity. Furthermore, the combination treatment of ZOL and ALF corrected the decrease in serum calcium and increase in serum alkaline phosphatase and the tartarate-resistant acid phosphatase level better than single-drug therapy using ZOL or ALF in OVX rats. In addition, the combination treatment of ZOL and ALF corrected the increase in urine calcium, phosphorous and creatinine levels better than single-drug therapy using ZOL or ALF in OVX rats.

Conclusions

These data suggest that the combination treatment of ZOL and ALF has a therapeutic advantage over each monotherapy for the treatment of osteoporosis.

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Acknowledgments

The authors are thankful to Mr. B.K. Jain, Naprod Life Sciences, Maharashtra, India, for providing the gift sample of zoledronic acid. The authors also gratefully acknowledge the contribution of Dr. M.R. Bhat, Mr. Vijay Kumar and Mr. Manish Kumar Priydarshi from Department of Aerospace Engineering, Indian Institute of Science, in carrying out the X-ray imaging and three point-bending tests. Helpful discussions on Micro-CT analysis with Dr. V. Kalliyana Krishnan of Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, are also gratefully acknowledged.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmacology, Al-Ameen College of Pharmacy, Bangalore, 560027, India

    Deepak Kumar Khajuria & Rema Razdan

  2. Department of Aerospace Engineering, Indian Institute of Science, Bangalore, 560012, India

    Deepak Kumar Khajuria & Debiprosad Roy Mahapatra

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  1. Deepak Kumar Khajuria
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  2. Rema Razdan
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  3. Debiprosad Roy Mahapatra
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Correspondence to Deepak Kumar Khajuria.

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Khajuria, D.K., Razdan, R. & Mahapatra, D.R. Zoledronic acid in combination with alfacalcidol has additive effects on trabecular microarchitecture and mechanical properties in osteopenic ovariectomized rats. J Orthop Sci 19, 646–656 (2014). https://doi.org/10.1007/s00776-014-0557-8

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  • DOI: https://doi.org/10.1007/s00776-014-0557-8

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