ABSTRACT
Several cases have been reported of unusual spontaneous fractures with minimal trauma in the subtrochanteric and diaphyseal areas of the femur linked to long-term bisphosphonate use. After encountering three such patients, we conducted a review of published cases. The average age of these individuals were 68 years and approximately 25% had received concomitant glucocorticoids. Histomorphometric bone biopsy studies performed in some individuals have suggested that severe suppression of bone turnover may be the underlying cause; however, cause and effect has not been firmly established. Moreover, population studies have found this type of fracture rare and not increased in patients who have received bisphosphonate treatment. Physicians should continue to use bisphosphonate agents as a primary treatment for osteoporosis.
Subject(s)
Bone and Bones/drug effects , Diphosphonates , Fractures, Spontaneous/etiology , Osteoporosis/complications , Osteoporosis/therapy , Adult , Aged , Aged, 80 and over , Biopsy , Bone Density Conservation Agents/administration & dosage , Bone Density Conservation Agents/adverse effects , Bone and Bones/metabolism , Bone and Bones/pathology , Diphosphonates/administration & dosage , Diphosphonates/adverse effects , Female , Femoral Fractures/diagnostic imaging , Femoral Fractures/etiology , Femoral Fractures/prevention & control , Fractures, Spontaneous/diagnostic imaging , Fractures, Spontaneous/prevention & control , Glucocorticoids/administration & dosage , Glucocorticoids/adverse effects , Humans , Male , Middle Aged , Osteoporosis/diagnostic imaging , Osteoporosis/metabolism , Osteoporosis/physiopathology , Primary Prevention , Radiography , Risk Factors , TimeABSTRACT
BACKGROUND: Studies suggest that testosterone (TT) replacement may have an antidepressant effect in depressed patients. OBJECTIVE: The objective of this study was to explore the effect of TT administration on depression using both a systematic review of the literature and a meta-analysis. METHODOLOGY: A search was conducted of MEDLINE, the Clinical Trials Registry, and Cochrane Central for English-language publications concerning randomized, placebo-controlled trials involving use of TT therapy in depressed patients. We searched for additional trials in the individual reference lists of the articles identified in the search. A study was judged to be relevant for inclusion in this review and meta-analysis if it reported original data from a controlled trial comparing use of TT and placebo in patients diagnosed with a depressive disorder according to DSM criteria, and the treatment response was evaluated according to changes on the Hamilton Rating Scale for Depression (HAM-D). We extracted the following data from the identified studies: study source, total number of participants in the study and in each treatment group, participants' ages, number of participants with a diagnosis of hypogonadism or HIV/AIDS, study duration, type of intervention, and change in HAM-D scores in the groups receiving TT versus placebo. The meta-analysis evaluated the effect of TT replacement on response in depressed patients as measured by change in HAM-D scores in the available placebo-controlled, randomized clinical trails. RESULTS: Seven studies (N=364) were identified that included a placebo-control group in a double-blind design. Eligibility criteria were clearly reported in all trials. Meta-analysis of the data from these seven studies showed a significant positive effect of TT therapy on HAM-D response in depressed patients when compared with placebo (z=4.04, P<0.0001). Subgroup analysis also showed a significant response in the subpopulations with hypogonadism (z=3.84, P=0.0001) and HIV/AIDS (z=3.33, P=0.0009) as well as in patients treated with TT gel (z=2.32, P=0.02). CONCLUSIONS: TT may have an antidepressant effect in depressed patients, especially those with hypogonadism or HIV/AIDS and elderly subpopulations. The route by which TT is administered may play a role in treatment response.
