Creative Biolabs has a wide spectrum of disease models for preclinical studies in different therapeutic areas and the capabilities to carry studies designed specifically for every research program. For the development of osteoporosis drugs, we offer both orchiectomy- and ovariectomy-induced osteoporosis models and a series of clinically relevant assessments.

Introduction of Male Osteoporosis Induced by Androgen Deficiency

Osteoporosis is a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue with a consequent increase in bone fragility and increased fracture risk. Male osteoporosis, which is characterized by an increase of bone resorption and was not recognized earlier, has now become an important public health issue with significant morbidity and mortality. Testosterone-replacement therapy is usually the main treatment choice for men with androgen-deficient osteoporosis. However, it is reported to be associated with an increased risk of prostate cancer and many other adverse effects, making it necessary and essential to find an alternative treatment which not only gives protection to the bone but at the same time possesses fewer side effects compared to the testosterone therapy.

The orchidectomized rodent model has been proposed to mimic male osteoporosis resulting from androgen deficiency. Typically, orchidectomy in rodents is performed via a scrotal approach, sometimes an abdominal approach can be used as well.

Introduction of the Scrotal Approach

Specifically, the anesthetized rat is placed supine on the operating table with its position fixed using sticking tape, the scrotal hair shaved, and the scrotum aseptically prepared. Then, a skin incision is made on the ventral side of the scrotum (0.5 cm for mice and 1.5 cm for rats) using a scalpel. The cremaster muscles are incised, and the testicular fat pad located at the entrance to the scrotal cavity is gently pulled through the incision using blunt forceps. The testicular content including the testis, cauda epididymis, the vas deferens, and the testicular blood vessels is gently exteriorized. Vas deferens and blood vessels are ligated with an absorbable suture, and the testis and epididymis are removed using small scissors. The remaining tissue is placed back in the scrotal sac using blunt forceps. Last, the cremaster muscle and scrotal skin are sutured layer by layer.

Orchiectomy-Induced Osteoporosis ModelFig.1 Methodology of orchidectomy.
(Blouin et al. 2008)

Features of Orchiectomy-Induced Osteoporosis Model

  • Orchidectomy results in a decrease of femoral and lumbar bone mineral density (BMD), a worsening of trabecular and cortical microarchitecture and a decrease in biomechanical properties.
  • The architectural changes in this model mimic those observed in hypogonadal men.
  • However, male rats exhibit a slightly slower rate of bone loss relative to female rats after removing gonadal tissues, suggesting that bone tissue in male rats might be less sensitive to sex hormone deficiency compared to female rats of similar age.

In testing the therapeutic efficacy of osteoporosis drug candidates, we are capable of conducting all kinds of assessments as well as providing assistance in data interpretation. Our battery of assessments including but not limited to:

  • Bone turnover markers
  • Serum/Urine calcium
  • Serum phosphorus
  • Bone mineral density (BMD)
  • Trabecular number, thickness
  • Mechanical tests
  • Trabecular bone volume fraction
  • Micro-CT
  • Histopathological analysis

Additionally, other examples of rodent musculoskeletal disease models that you may be interested include:

Creative Biolabs' pharmacology team has extensive drug discovery and development experiences in the pharmaceutical industry enabling us to support a range of flexible services, including study design and data interpretation. Besides, our expertise is also coupled with a commitment to develop customized models with our clients for their special requirements. Contact us now to discuss your specific requirements.

Reference

  1. Blouin.; et al. Orchidectomy Models of Osteoporosis. Osteoporosis. Humana Press. 2008:125-134.

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