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Enzalutamide Reduces the Bone Mass in the Axial but not the Appendicular Skeleton in Male Mice.

Artikel i vetenskaplig tidskrift
Författare Jianyao Wu
Sofia Movérare-Skrtic
Anna E Börjesson
Marie K Lagerquist
Klara Sjögren
Sara H Windahl
Antti Koskela
Louise Grahnemo
Ulrika Islander
Anna S K Wilhelmson
Åsa Tivesten
Juha Tuukkanen
Claes Ohlsson
Publicerad i Endocrinology
Volym 157
Nummer/häfte 2
Sidor 969-977
ISSN 1945-7170
Publiceringsår 2016
Publicerad vid Wallenberglaboratoriet
Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning
Centre for Bone and Arthritis Research
Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition
Sidor 969-977
Språk en
Länkar dx.doi.org/10.1210/en.2015-1566
Ämneskategorier Endokrinologi

Sammanfattning

Testosterone is a crucial regulator of the skeleton but the role of the androgen receptor (AR) for the maintenance of the adult male skeleton is unclear. In the present study, the role of the AR for bone metabolism and skeletal growth after sexual maturation was evaluated by means of the drug enzalutamide, which is a new AR antagonist used in the treatment of prostate cancer patients. Nine-week-old male mice were treated with 10, 30, or 100 mg/kg/day of enzalutamide for 21 days or were surgically castrated, and compared with vehicle-treated gonadal intact mice. Although orchidectomy (orx) reduced the cortical bone thickness and trabecular bone volume fraction in the appendicular skeleton, these parameters were unaffected by enzalutamide. In contrast, both enzalutamide and orx reduced the bone mass in the axial skeleton as demonstrated by reduced lumbar spine areal bone mineral density (p<0.001) and trabecular bone volume fraction in L5 vertebrae (p<0.001) compared with vehicle-treated gonadal intact mice. A compression test of the L5 vertebrae revealed that the mechanical strength in the axial skeleton was significantly reduced by enzalutamide (maximal load at failure, -15.3±3.5%; p<0.01). The effects of enzalutamide in the axial skeleton were associated with a high bone turnover. In conclusion, enzalutamide reduces the bone mass in the axial but not the appendicular skeleton in male mice after sexual maturation. We propose that the effect of testosterone on the axial skeleton in male mice is mainly mediated via the AR.

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