Denosumab steroid induced osteoporosis

In large studies, women taking bisphosphonates for osteoporosis have had unusual fractures ("bisphosphonate fractures") in the femur (thigh bone) in the shaft ( diaphysis or sub-trochanteric region) of the bone, rather than at the femoral neck, which is the most common site of fracture. However, these unusual fractures are extremely rare (12 in 14,195 women) compared to the common hip fractures (272 in 14,195 women), and the overall reduction in hip fractures caused by bisphosphonate far outweighed the unusual shaft fractures. [32] There are concerns that long-term bisphosphonate use can result in over-suppression of bone turnover . It is hypothesized that micro-cracks in the bone are unable to heal and eventually unite and propagate, resulting in atypical fractures. Such fractures tend to heal poorly and often require some form of bone stimulation, for example bone grafting as a secondary procedure. This complication is not common, and the benefit of overall fracture reduction still holds. [32] [33] In cases where there is concern of such fractures occurring, teriparatide is potentially a good alternative because it does not cause as much damage as a bisphosphonate does by suppressing bone turnover. [34]

Reid et al (2005) reported on the results of 2 double-blind, placebo-controlled clinical studies of zoledronic acid in the treatment of Paget disease of the bone.  In these studies, one 15-min infusion of 5 mg of zoledronic acid was compared to 60 days of oral risedronate (Actonel) (30 mg per day) in a total of 347 patients with Paget disease of the bone.  The primary efficacy end point was the rate of therapeutic response at 6 months, defined as a normalization of alkaline phosphatase levels or a reduction of at least 75 % in the total alkaline phosphatase excess.  At 6 months, % of patients receiving zoledronic acid achieved a therapeutic response, as compared with  % of patients receiving risedronate, a difference that was statistically significant.  The investigators reported that alkaline phosphatase levels normalized in  % of patients in the zoledronic acid group and  % of patients in the risedronate group (p < ).  Zoledronic acid was associated with a shorter median time to a first therapeutic response (64 days versus 89 days, p < ).  The investigators reported that the physical-component summary score of the Medical Outcomes Study 36-item Short-Form General Health Survey, a measure of the quality of life, increased significantly from baseline at both 3 and 6 months in the zoledronic acid group and differed significantly from those in the risedronate group at 3 months.  The investigators noted that pain scores improved in both groups.  During post-trial follow-up (median of 190 days), 21 of 82 patients in the risedronate group had a loss of therapeutic response, as compared with 1 of 113 patients in the zoledronic acid group (p < ).  The investigators concluded that a single infusion of zoledronic acid produces more rapid, more complete, and more sustained responses in Paget disease than does daily treatment with risedronate.

Glucocorticoid therapy is associated with an appreciable risk of bone loss, which is most pronounced in the first few months of use. In addition, glucocorticoids increase fracture risk, and fractures occur at higher bone mineral density (BMD) values than occur in postmenopausal osteoporosis. The increased risk of fracture has been reported with doses of prednisone or its equivalent as low as to mg daily [ 1 ]. Thus, glucocorticoid-induced bone loss should be treated aggressively, particularly in those already at high risk for fracture (older age, prior fragility fracture). In other individuals, clinical risk factor and bone density assessment may help guide therapy. The prevention and treatment of glucocorticoid-induced bone loss will be reviewed here. The clinical features are reviewed separately. (See "Clinical features and evaluation of glucocorticoid-induced osteoporosis" .)

Childhood cerebral adrenoleukodystrophy (ALD) is a severe neurologic disease that rapidly progresses to total disability and death unless treated with allogeneic hematopoietic cell transplantation (HCT), which has considerable morbidity and mortality. Gene therapy with autologous hematopoietic stem cells is emerging as a possible alternative treatment. A study of 17 boys with early-stage cerebral ALD enrolled to undergo transplantation with autologous CD34+ cells transfected with Lenti-D (a lentiviral vector containing manufactured ABCD1 complementary DNA) reported 88 percent were alive with no major functional disabilities at 24 months posttransplantation [ 14 ]. One boy died from disease progression that began during pretransplantation conditioning, and one was withdrawn from the study and died from complications of subsequent allogeneic HCT. None of the survivors had evidence of graft failure or graft-versus-host disease. These results suggest that autologous hematopoietic stem cell gene therapy may be as effective as, and safer than, HCT for treatment of early cerebral ALD. The treatment has not received regulatory approval. The clinical trial is ongoing and important uncertainties remain. (See "Adrenoleukodystrophy", section on 'Gene therapy' .)

Denosumab steroid induced osteoporosis

denosumab steroid induced osteoporosis

Childhood cerebral adrenoleukodystrophy (ALD) is a severe neurologic disease that rapidly progresses to total disability and death unless treated with allogeneic hematopoietic cell transplantation (HCT), which has considerable morbidity and mortality. Gene therapy with autologous hematopoietic stem cells is emerging as a possible alternative treatment. A study of 17 boys with early-stage cerebral ALD enrolled to undergo transplantation with autologous CD34+ cells transfected with Lenti-D (a lentiviral vector containing manufactured ABCD1 complementary DNA) reported 88 percent were alive with no major functional disabilities at 24 months posttransplantation [ 14 ]. One boy died from disease progression that began during pretransplantation conditioning, and one was withdrawn from the study and died from complications of subsequent allogeneic HCT. None of the survivors had evidence of graft failure or graft-versus-host disease. These results suggest that autologous hematopoietic stem cell gene therapy may be as effective as, and safer than, HCT for treatment of early cerebral ALD. The treatment has not received regulatory approval. The clinical trial is ongoing and important uncertainties remain. (See "Adrenoleukodystrophy", section on 'Gene therapy' .)

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