Jaime Kulak Júnior

Osteoporosis After Transplantation

Transplantation is an established therapy for end-stage diseases of kidney, lung, liver, and heart among others. Osteoporosis and fragility fractures are serious complications of organ transplantation, particularly in the first post-transplant year. Many factors contribute to the pathogenesis of osteoporosis following organ transplantation. This review addresses the mechanisms of bone loss that occurs both in the early and late post-transplant periods, including the contribution of the immunosuppressive agents as well as the specific features to bone loss after kidney, lung, liver, cardiac, and bone marrow transplantation. Prevention and treatment for osteoporosis in the transplant recipient are also discussed.

Post-transplantation osteoporosis

Osteoporosis is prevalent in transplant recipients and is related to pre- and post-transplantation factors. Low bone density and fractures may antedate transplantation, related to traditional risk factors for osteoporosis, effects of chronic illness, and end-stage organ failure and its therapy, on the skeleton. Bone loss after transplantation is related to adverse effects of immunosuppressive drugs (glucocorticoids and calcineurin inhibitors) on bone remodeling. Newer immunosuppressive medications may permit lower doses of glucocorticoids and may be associated with decreased bone loss and fractures. Bisphosphonates are currently the most effective agents for the prevention and treatment of post-transplantation osteoporosis.

Bone disease after transplantation: osteoporosis and fractures risk

Organ transplantation is the gold standard therapy for several end-stage diseases. Bone loss is a common complication that occurs in transplant recipients. Osteoporosis and fragility fractures are serious complication, mainly in the first year post transplantation. Many factors contribute to the pathogenesis of bone disease following organ transplantation. This review address the mechanisms of bone loss including the contribution of the immunosuppressive agents as well as the specific features to bone loss after kidney, lung, liver, cardiac and bone marrow transplantation. Prevention and management of bone loss in the transplant recipient should be included in their post transplant follow-up in order to prevent fractures.

SERMs in the prevention and treatment of postmenopausal osteoporosis: an update

Selective estrogen receptor modulators (SERMs) have the ability to bind the estrogen receptor (ER) and are known to confer ER agonist or antagonist effects depending on the target tissue. A number of newer SERMs, including bazedoxifene, lasofoxifene and ospemifene, are currently under clinical development for the prevention and treatment of postmenopausal osteoporosis and for other indications. Although the possibility of developing a single agent that has all of the desired characteristics of an ideal SERM seems to be unlikely, progress in the clinical development of SERMs targeted to the ER suggests that these newer compounds may have attributes that represent an improvement relative to existing SERMs. A new approach to menopausal therapy is the tissue selective estrogen complex or the pairing of a selective estrogen receptor modulator with estrogens. Further investigation will help to clarify relative benefits/risks of novel SERMs in development within specific indications.

Androgênios séricos e densidade mineral óssea em mulheres ooforectomizadas e não ooforectomizadas na pós-menopausa

OBJECTIVE Compare levels of androgens and bone mineral density (BMD) of ovariectomized (OVX) and non-ovariectomized (NOVX) postmenopausal women. Forty women, 20 OVX and 20 NOVX, (53.9 +/- 4 years) were selected. METHODS Total testosterone (TT), free testosterone (FT), androstenedione (AN), dehidroepiandrostenedione (DHEA) and its sulfate (DHEA-S) were measured. BMD was measured in 14 OVX and 16 NOVX. RESULTS No differences between groups with regard to age, body mass index (BMI) and time since menopause were found. Mean levels of TT and FT were two-fold higher in NOVX group (60.91 versus 30.17 ng/dL, p = 0.0001; 1.00 versus 0.48 pg/mL, p = 0.003). BMD was not different between groups. Inverse correlations were found between BMI and TT (r = -0.3; p = 0.05); time since menopause and AN (r = -0.35; p = 0.02) and time since menopause and DHEA (r = -0.3; p = 0.01). CONCLUSION Bilateral ovariectomy leads to a more severe androgen deficiency than natural menopause in postmenopausal women and did not compromise bone mass.

Função ovariana em mulheres lúpicas submetidas ao uso de ciclofosfamida em dois grandes centros de atendimento reumatológico de Curitiba, Estado do Paraná

PURPOSE: To evaluate the ovarian response after cyclophosphamide use (CPM) in patients with systemic lupus erythematosus (SLE) and to correlate the age and cumulative dose findings with changes in menstrual cycle and/or progression to ovarian failure (OF). METHODS: This was a cross-sectional, retrospective study of 50 patients with a diagnosis of SLE who used CFM with a clinical follow-up of at least 1 year. Included were patients aged 12-40 years, who had undergone chemotherapy for SLE control and who had regular menstrual cycles before the beginning of CPM treatment. Patients who discontinued follow-up, who were followed up for less than one year or who had irregular/absent menses before the beginning of CPM treatment were excluded. All women studied were submitted to an interview and a questionnaire containing questions about the pattern of the menstrual cycle before and after therapy, and about the gestational periods and contraception. We asked if the patients had been instructed about the side effects and consequences of CFM. Statistical analysis was performed using the Student t-test and the Mann Whitney, χ2 and nonparametric Kolmogorov-Smirnov tests. RESULTS: The mean age of the patients included in the study was 30.8 years and the mean age at the time of use of CPM was 25.3 years. After CFM, 24% of patients stopped menstruating, 28% returned to regular cycles and 48% continued to have irregular cycles. It was found that the patients who developed OF had longer disease duration (12.3 years) than those who did not develop it (8.9 years). Thirteen patients became spontaneously pregnant after CFM; however, 66% progressed to abortion. The mean age of the patients who used CFM and developed OF was 28.1 years. Amenorrhea occurred in 50% of those aged 31-40 years, in 22.2% of those aged 21-30 years and in 7.7% of those aged 12-20 years. Our study showed no statistical correlation between cumulative dose and OF, although cumulative doses greater than 11grams tended to promote some type of menstrual irregularity. CONCLUSION: SLE disease duration, age at the time of treatment and the highest cumulative doses are important predictors of OF after therapy with CFM. Pregnancy in lupus patients is more likely to evolve with abortion after the use of chemotherapy. It was seen that a small proportion of patients were aware of all the implications of the drug. Therefore, additional studies should be conducted for further knowledge and awareness of the importance of contraception and the preservation of ovarian tissue on the part of the medical community.

Safety, Efficacy and Patient Acceptability of Bazedoxifene Acetate in the Management of Postmenopausal Osteoporosis

Many pharmacological agents are available for treatment of postmenopausal osteoporosis, including estrogen and the selective modulators of estrogen receptor (SERMS). Bazedoxifene is a third-generation SERM, which acts as estrogen agonist in bone and lipid metabolism and as an antagonist in the breast and endometrium. Studies demonstrated that bazedoxifene reduced significantly the risk of vertebral fractures. In a subgroup of patients at high risk (post-hoc analysis), a reduction of nonvertebral fractures risk was reported. Moreover, the combination of conjugated estrogens with bazedoxifene seems to offer an alternative to classical hormone therapy, improving the vasomotor symptoms and vaginal atrophy, without the use of a progestin. Bazedoxifene is a promising drug for the treatment and prevention of osteoporosis in postmenopausal women; however a safety concern regarding venous thromboembolic events is needed before starting treatment.