The effects of long-term raloxifene and estradiol treatments on bone in a patient with congenital aromatase deficiency.
BACKGROUND
In adult aromatase-deficient men, estrogen treatment has always resulted in a rapid skeletal maturation with epiphyseal closure and improved BMD. Raloxifene is a SERM with proven estrogen agonist action on bone that leads to an improvement in BMD and a reduction in bone turnover. The present study reports the effects of raloxifene and transdermal estradiol treatment, respectively, on epiphyseal closure and BMD in an aromatase-deficient man, over a 24-month follow-up, with the aim of obtaining further insight into the role of estrogens in the male skeletal homeostasis.


METHODS
A 25-year-old Caucasian man with aromatase deficiency, a bone age of 15.3 years, unfused epiphyses and an impaired BMD was initially administered raloxifene (60 mg/day per os) for 12 months, while transdermal estradiol (25 microg twice weekly) was administered for the subsequent 12 months. During the follow-up, the effects of the two treatments on epiphyseal closure, BMD and bone turnover markers were investigated. An iliac crest bone biopsy was performed only before and after the raloxifene treatment, but it was not repeated after transdermal estradiol treatment.


RESULTS
No changes in bone age were observed after raloxifene therapy, whereas a complete epiphyseal closure was achieved with transdermal estradiol treatment. Compared with baseline values, raloxifene treatment led to improved BMD both at the ultradistal forearm and 33% radius; the transdermal estradiol treatment resulted in a further slight increase in BMD at the 33% radius, but not at the ultradistal forearm. The baseline bone biopsy showed elevated bone remodelling in trabecular bone, while the second biopsy following raloxifene treatment revealed a decrease in remodelling.


CONCLUSIONS
This study shows that the management of aromatase deficiency in the male cannot consider raloxifene as a first choice treatment, but should be still based on estrogen replacement treatment since in this patient the completion of bone maturation has only been obtained once estradiol substitution was performed. The present case also demonstrates that raloxifene is able to improve BMD in aromatase-deficient men.
Integrated Department of Medicine, Endocrinology, Metabolism, and Geriatrics, University of Modena and Reggio Emilia, Via Giardini 1355, 41100 Modena, Italy.
L
L
Zirilli
L
L
Maffei
P J
PJ
Meunier
P
P
Chavassieux
C
C
Carani
V
V
Rochira
D000328:Adult; D001141:Aromatase / Q000172:deficiency*; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004838:Epiphyses / Q000000981:diagnostic imaging / Q000187:drug effects; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D012739:Gonadal Steroid Hormones / Q000097:blood; D006066:Gonads / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D011859:Radiography; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D012739:Gonadal Steroid Hormones; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D001141:Aromatase