Testosterone Plus Finasteride Prevents Bone Loss without Prostate Growth in a Rodent Spinal Cord Injury Model.
We have reported that testosterone-enanthate (TE) prevents the musculoskeletal decline occurring acutely after spinal cord injury (SCI), but results in a near doubling of prostate mass. Our purpose was to test the hypothesis that administration of TE plus finasteride (FIN; type II 5α-reductase inhibitor) would prevent the chronic musculoskeletal deficits in our rodent severe contusion SCI model, without inducing prostate enlargement. Forty-three 16-week-old male Sprague-Dawley rats received: 1) SHAM surgery (T9laminectomy); 2) severe (250 kdyne) contusion SCI; 3) SCI+TE (7.0 mg/week, intramuscular); or 4) SCI+TE+FIN (5 mg/kg/day, subcutaneous). At 8 weeks post-surgery, SCI animals exhibited reduced serum testosterone and levator ani/bulbocavernosus (LABC) muscle mass, effects that were prevented by TE. Cancellous and cortical (periosteal) bone turnover (assessed by histomorphometry) were elevated post-SCI, resulting in reduced distal femur cancellous and cortical bone mass (assessed by microcomputed tomography). TE treatment normalized cancellous and cortical bone turnover and maintained cancellous bone mass at the level of SHAM animals, but produced prostate enlargement. FIN coadministration did not inhibit the TE-induced musculoskeletal effects, but prevented prostate growth. Neither drug regimen prevented SCI-induced cortical bone loss, although no differences in whole bone strength were present among groups. Our findings indicate that TE+FIN prevented the chronic cancellous bone deficits and LABC muscle loss in SCI animals without inducing prostate enlargement, which provides a rationale for the inclusion of TE+FIN in multimodal therapeutic interventions intended to alleviate the musculoskeletal decline post-SCI.
1 Research Service, Malcom Randall Department of Veterans Affairs Medical Center , North Florida/South Georgia Veterans Health System, Gainesville, Florida.|2 Department of Applied Physiology and Kinesiology, University of Florida , Gainesville, Florida.
Joshua F
JF
Yarrow
1 Research Service, Malcom Randall Department of Veterans Affairs Medical Center , North Florida/South Georgia Veterans Health System, Gainesville, Florida.
Ean G
EG
Phillips
1 Research Service, Malcom Randall Department of Veterans Affairs Medical Center , North Florida/South Georgia Veterans Health System, Gainesville, Florida.
Christine F
CF
Conover
1 Research Service, Malcom Randall Department of Veterans Affairs Medical Center , North Florida/South Georgia Veterans Health System, Gainesville, Florida.
Taylor E
TE
Bassett
3 Department of Orthopedics and Rehabilitation, University of Florida , Gainesville, Florida.
Cong
C
Chen
3 Department of Orthopedics and Rehabilitation, University of Florida , Gainesville, Florida.
Tyler
T
Teurlings
1 Research Service, Malcom Randall Department of Veterans Affairs Medical Center , North Florida/South Georgia Veterans Health System, Gainesville, Florida.
Andrea
A
Vasconez
1 Research Service, Malcom Randall Department of Veterans Affairs Medical Center , North Florida/South Georgia Veterans Health System, Gainesville, Florida.
Jonathan
J
Alerte
1 Research Service, Malcom Randall Department of Veterans Affairs Medical Center , North Florida/South Georgia Veterans Health System, Gainesville, Florida.
Hannah
H
Prock
4 Physiological Sciences, University of Florida , Gainesville, Florida.
Jessica M
JM
Jiron
1 Research Service, Malcom Randall Department of Veterans Affairs Medical Center , North Florida/South Georgia Veterans Health System, Gainesville, Florida.
Micah
M
Flores
4 Physiological Sciences, University of Florida , Gainesville, Florida.
J Ignacio
JI
Aguirre
1 Research Service, Malcom Randall Department of Veterans Affairs Medical Center , North Florida/South Georgia Veterans Health System, Gainesville, Florida.|2 Department of Applied Physiology and Kinesiology, University of Florida , Gainesville, Florida.
Stephen E
SE
Borst
1 Research Service, Malcom Randall Department of Veterans Affairs Medical Center , North Florida/South Georgia Veterans Health System, Gainesville, Florida.
Fan
F
Ye
D058891:5-alpha Reductase Inhibitors / Q000494:pharmacology; D000728:Androgens / Q000494:pharmacology; D000818:Animals; D016723:Bone Remodeling / Q000187:drug effects*; D001862:Bone Resorption / Q000209:etiology / Q000517:prevention & control; D004195:Disease Models, Animal; D018120:Finasteride / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects; D011467:Prostate / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000150:complications*; D013739:Testosterone / Q000031:analogs & derivatives* / Q000494:pharmacology
D058891:5-alpha Reductase Inhibitors; D000728:Androgens; D013739:Testosterone; D018120:Finasteride; C004648:testosterone enanthate
5α; androgen; dihydrotestosterone; hypogonadism; osteoporosis; reductase