Long-term Glucocorticoid Therapy Research Articles

G.P.97 : Prophylactic oral bisphosphonate therapy in Duchenne muscular dystrophy: The Newcastle upon Tyne experience

Duchenne muscular dystrophy (DMD) is an X-linked condition characterized by progressive muscle weakness. Glucocorticoids (GC) are a key pharmacological intervention that is associated with prolonged ambulation, reduction of scoliosis and better-preserved respiratory function. However long-term GC therapy, in particular daily regimens, is a significant risk factor for osteoporosis and vertebral fractures. While bisphosphonates (BP) are recommended in case of fractures, prophylactic use of BP remains controversial. Here we summarize our experience of prophylactic BP therapy on a group of DMD patients on daily GC on follow up at the paediatric neuromuscular clinic in Newcastle upon Tyne. Patients were offered prophylactic BP (oral Risedronate) under the guidance of the local paediatric endocrinology team from January 2008. Patients were reviewed 6 monthly for tolerability, side effects, bone pain, frequency of fractures and impact on bone mineral density (BMD) determined by yearly DXA analysis. Vitamin D supplementation (800–1000IU/L daily) was provided and insufficiencies/deficiencies were treated. Out of a total of 52 patients included in this study, 9 stopped treatment because of side effects (in particular abdominal or joint pain and flu like symptoms). 43 boys continued BP therapy for an average of 24months (range 12–54months). Median lumbar spine adjusted BMD (BMAD) Z-scores remained stable during treatment, being 0.11 at baseline and 0.21 at the 3rd year follow up. Z-scores for total body mineral content (minus head) were stable during the period of treatment. 7 patients suffered long bone fracture during therapy and 3 had vertebral fractures (VF), the majority having been on GC for >36months at the time of fracture. Patients who suffered VF all had lumbar spine BMAD Z-scores <−1 at baseline. In summary, our results indicate that prophylactic BPs therapy is well tolerated by most patients and may have a role in preventing steroid-induced osteoporosis in DMD.

The Past versus the Present, 1980-2004: Reduction of Mean Initial Low-Dose, Long-Term Glucocorticoid Therapy in Rheumatoid Arthritis from 10.3 to 3.6 mg/Day, Concomitant with Early Methotrexate, with Long-Term Effectiveness and Safety of Less than 5 mg/Day

Quantitative observations are presented concerning treatment with glucocorticoids of 308 patients with rheumatoid arthritis (RA) at a weekly academic rheumatology setting over 25 years from 1980 to 2004. A database of all visits included medications and multidimensional health assessment questionnaire scores for physical function, pain and routine assessment of patient index data (RAPID3; and a surrogate RAPID3-EST), completed by each patient at each visit in routine care. Over the 5-year periods of 1980-1984, 1985-1989, 1990-1994, 1995-1999 and 2000-2004, the mean initial prednisone daily dose declined from 10.3 to 6.5, 5.1, 4.1 and 3.6 mg/day, as initial doses were >5 mg/day in 49, 16, 7, 7 and 3% of patients, 5 mg/day in 51, 80, 70, 26 and 10%, and <5 mg/day in 0, 4, 23, 67 and 86%. Reduction of prednisone doses in the respective five-year periods was accompanied by increased and earlier use of methotrexate as the first disease-modifying antirheumatic drug (DMARD) in 10, 26, 57, 71 and 78%, and methotrexate treatment in 10, 26, 74, 82 and 92% of patients within the first year of disease. Higher methotrexate doses in the respective five-year periods were used after 1990, along with lower prednisone doses. Most patients were treated indefinitely with both low-dose prednisone and methotrexate; 80% continued both medications for more than 5 years. The primary adverse events were skin-thinning and bruising. New hypertension, diabetes and cataracts were seen in fewer than 10% of patients. While efficacy and safety cannot be analyzed definitively from observational data, the data suggest that many patients with RA might be treated effectively with weekly low-dose methotrexate along with initial and long-term, low-dose prednisone of <5 mg/day.

A survey of steroid-related osteoporosis diagnosis, prevention and treatment practices of pediatric rheumatologists in North America.

BackgroundThe purpose of our study is to assess practices of North American pediatric rheumatologists regarding monitoring, prevention, and treatment of low bone mineral density (BMD) in children on long-term glucocorticoid treatment.Long-term glucocorticoid therapy is associated with accelerated bone loss. Children with JIA and lupus have low baseline BMD and incident vertebral fractures commonly occur in these groups of patients even after a relatively short period of time being on systemic glucocorticoids. There are no established guidelines for identification, prevention, and treatment of glucocorticoid-induced bone loss in children.MethodsA cross-sectional online survey was conducted with 199 physicians who were listed in the ACR database as practicing pediatric rheumatology in North America.Results86 physicians (43%) responded; 87% were board-certified in pediatric rheumatology. 95% used dual energy X-ray absorptiometry as their primary modality for assessing BMD. 79% “rarely” or “never” obtained a baseline BMD measurement prior to initiation of glucocorticoid therapy. 42% of respondents followed BMD annually. 93% “frequently” or “always” prescribed calcium for patients on long-term corticosteroid therapy; 81% “frequently” or “always” prescribed vitamin D. In patients diagnosed with osteoporosis, 35%-50 % of the practitioners “sometimes”, “frequently” or “always” prescribed bisphosphonates. Bisphosphonates are prescribed at similar rates for male and female patients, and slightly more frequently for pubertal than for pre-pubertal patients. 96% of respondents “rarely” or “never” prescribed calcitonin for patients on long-term glucocorticoid therapy; 92% “rarely” or “never” prescribe this medication for patients with known osteopenia or osteoporosis.ConclusionsUtilization of DXA in children on long-term corticosteroid therapy varies greatly among North American pediatric rheumatologists. Most respondents do not screen for low BMD on a regular basis despite acknowledging the risks of bone loss in this population. Broad consensus appears to be present among practitioners favoring the prescription of calcium and vitamin D for patients receiving long-term corticosteroid therapy. Relatively few respondents consistently recommend bisphosphonate therapy, even for patients with known low bone density; calcitonin is rarely used. These data underscore the need for studies to acquire specific data on bone loss, and its prevention and treatment in young patients on long-term glucocorticoid therapy.

Why Rate of BMD Loss Does Not Predict Fracture Risk: The “Yogi Berra” Principle

than the general population. Rheumatoid arthritis (RA) is a chronic inflammatory rheumatic disease and a frequent cause of secondary osteoporosis induced by the chronic inflammatory condition and a long-term glucocorticoid therapy (GC). The aim of this study is to evaluate the influence of GC on the trabecular bone score (TBS), BMD and TBS dynamics during one year in patients with RA. Methods: 134 examined women with RA (age 52.5 12.8 years; height 162.6 6.4 cm, weight 68.2 13.7 kg, duration of disease 9.1 7.5 years, duration of postmenopausal period 7.6 7.2 years) were divided into three groups: first group, G1e37 patients who did not use GC; second group, G2e 50 patients who used GC in a dose of O5 mg of prednisolone for more than 3 years; third group, G3 e 47 patients who took GC only at the exacerbated stage for!6 months. All the patients had been takingmethotrexate as a basic treatment. BMD of total body, PA lumbar spine, proximal femur and forearm were measured using the DXA method (Prodigy, GEHC Lunar, Madison,WI, USA) and PA spine TBSwas assessed bymeans of TBS iNsight software package installed on our DXA machine (Med-Imaps, Pessac, France). Evaluation of TBS dynamics in the patients of G1 and G2 groups during the year was conducted on the background of ongoing therapy which included doses of GC (for the patients of second group) and/or without any osteotropic treatment. Results: The 3 groups did not differ as to age, basic anthropometric parameters, duration of disease and duration of postmenopausal period in these groups. TBS in G2 was significantly lower compared to G1 (TBSL1-L4: 1.147 0.168 vs. 1.250 0.135; t5-3.07; p50.003), and G3 compared to G1 (TBS L1-L4: 1.274 0.138; t53.95; p50.0002). However, there were no differences in BMD of PA spine and hip among groups. Only forearm BMD in the second group was significantly lower compared to the first one (0.583 0.176 g/cm vs. 0.675 0.229 g/cm; t5-2.18; p50.032). Spine TBS decreased by 1.4% after one year for G1 and by 5.8% for G2. Conclusion: For patients who are GC users, TBS, but not BMD, reflects bone microarchitecture deterioration which is an indicator for those patients to of a higher vertebrae and nonvertebral risk of fracture. TBS is a determinant of bone state and must be monitored during the long-term treatment with GC. Disclosure of Interest: None Declared

Denosumab May Warrant Further Testing in Patients Receiving Long-Term GC Therapy

Although glucocorticoids (GCs) are a backbone of the treatment of rheumatic diseases, they are the major cause of secondary osteoporosis and are associated with increased fracture rate and decreased bone quality. This article discusses outcomes from Denosumab in Current Users of Bisphosphonates for Glucocorticoid-Induced Osteoporosis [NCT01465568].

Drug-induced tendinopathy: From physiology to clinical applications

Drug-induced tendon toxicity is rare but often underestimated. To date, four main drug classes have been incriminated in tendinopathies. Quinolones and long-term glucocorticoids are the most widely known, but statins and aromatase inhibitors can also induce tendon damage. The specific pathophysiological mechanisms responsible for drug-induced tendinopathies remain unknown. Proven risk factors have been identified, such as age older than 60years, pre-existing tendinopathy, and potentiation of toxic effects when several drug classes are used in combination. Mean time to symptom onset varies from a few days with quinolones to several months with statins and several years for long-term glucocorticoid therapy. The most common sites of involvement are the lower limb tendons, most notably the body of the Achilles tendon. The first part of this review discusses tendon anatomy and the pathophysiology and radiological manifestations of tendinopathies. The second part provides details on the main characteristics of each of the drugs classes associated with tendon toxicity.

AB0454 Comparative Analysis of Periprosthetic Fractures of Hip and Knee Arthroplasty in Patients with Rheumatic Diseases

BackgroundSurgical treatment of patients with rheumatic diseases (RD) is associated with increased risk of complications. It is caused presence of an inflammatory process, osteoporosis, the reduced physical activity, the severity...

SAT0068 Influence of Glucocorticoids on Trabecular Bone Score in Patients with Rheumatoid Arthritis

BackgroundBone disorders are the main extra-articular complications of rheumatoid arthritis (RA). Patients with RA have a greater risk of osteoporosis and fracture than the general population. Rheumatoid arthritis (RA) is...

SAT0277 Has Shoulder Ultrasonography Got A Predictive Value in Polymialgia Rheumatica?

BackgroundPolymyalgia rheumatica (PMR) is an inflammatory condition characterized by aching and morning stiffness in the shoulders, hip girdle, and neck. The initial goal of therapy is to rapidly achieve symptomatic...

Dexamethasone shifts bone marrow stromal cells from osteoblasts to adipocytes by C/EBPalpha promoter methylation

Dexamethasone (Dex)-induced osteoporosis has been described as the most severe side effect in long-term glucocorticoid therapy. The decreased bone mass and the increased marrow fat suggest that Dex possibly shifts the differentiation of bone marrow stromal cells (BMSCs) to favor adipocyte over osteoblast, but the underlying mechanisms are still unknown. In this paper, we established a Dex-induced osteoporotic mouse model, and found that BMSCs from Dex-treated mice are more likely to differentiate into adipocyte than those from control mice, even under the induction of bone morphogenetic protein-2 (BMP2). We also discovered both in vitro and in vivo that the expression level of adipocyte regulator CCAAT/enhancer-binding protein alpha (C/EBPalpha) is significantly upregulated in Dex-induced osteoporotic BMSCs during osteoblastogenesis by a mechanism that involves inhibited DNA hypermethylation of its promoter. Knockdown of C/EBPalpha in Dex-induced osteoporotic cells rescues their differentiation potential, suggesting that Dex shifts BMSC differentiation by inhibiting C/EBPalpha promoter methylation and upregulating its expression level. We further found that the Wnt/beta-catenin pathway is involved in Dex-induced osteoporosis and C/EBPalpha promoter methylation, and its activation by LiCl rescues the effect of Dex on C/EBPalpha promoter methylation and osteoblast/adipocyte balance. This study revealed the C/EBPalpha promoter methylation mechanism and evaluated the function of Wnt/beta-catenin pathway in Dex-induced osteoporosis, providing a useful therapeutic target for this type of osteoporosis.

Implications of combined ovariectomy and glucocorticoid (dexamethasone) treatment on mineral, microarchitectural, biomechanical and matrix properties of rat bone.

Osteoporosis is one of the deleterious side effects of long-term glucocorticoid therapy. Since the condition is particularly aggressive in postmenopausal women who are on steroid therapy, in this study we have attempted to analyse the combined effect of glucocorticoid (dexamethasone) treatment and cessation of oestrogen on rat bone. The dual aim was to generate osteoporotic bone status in a short time scale and to characterise the combination of glucocorticoid-postmenopausal osteoporotic conditions. Sprague Dawley rats (N = 42) were grouped randomly into three groups: untreated control, sham-operated and ovariectomized-steroid (OVX-Steroid) rats. Control animals were euthanized with no treatment [Month 0 (M0)], while sham and OVX-Steroid rats were monitored up to 1 month (M1) and 3 months (M3) post laparotomy/post OVX-Steroid treatment. Histology, dual-energy X-ray absorptiometry (DXA), micro-computed tomography (micro-CT), and biomechanical and mRNA expression analysis of collagenous, non-collagenous matrix proteins and osteoclast markers were examined. The study indicated enhanced osteoclastogenesis and significantly lower bone mineral density (BMD) in the OVX-Steroid rats with Z-scores below -2.5, reduced torsional strength, reduced bone volume (BV/TV%), significantly enhanced trabecular separation (Tb.S), and less trabecular number (Tb.N) compared with sham rats. Osteoclast markers, cathepsin K and MMP 9 were upregulated along with Col1α1 and biglycan with no significant expression variation in fibronectin, MMP 14, LRP-5, Car II and TNC. These results show higher bone turnover with enhanced bone resorption accompanied with reduced torsional strength in OVX-Steroid rats; and these changes were attained within a short timeframe. This could be a useful model which mimics human postmenopausal osteoporosis that is associated with steroid therapy and could prove of value both in disease diagnosis and for testing generating and testing biological agents which could be used in treatment.

Secondary osteoporosis or secondary contributors to bone loss in fracture. Therapeutic strategy for glucocorticoid-induced osteoporosis

Glucocorticoid is widely used to treat a variety of diseases and causes a number of significant side effects. Glucocorticoid-induced osteoporosis (GIOP) is known as a serious adverse effect during long-term glucocorticoid therapy. Guideline in Japan recommends bisphosphonates as first-line drugs. Bisphosphonates increase bone mineral density (BMD) and reduce vertebral fracture risk in patient beginning or continuing glucocorticoid treatment. As well as increased bone resorption, GIOP could induce severe suppression of bone formation. Although bisphosphonates are effective for GIOP, anabolic therapeutic strategies should be considered as alternative therapy in GIOP. Teripatratide (PTH (1-34) ) , a bone anabolic drug, is widely used in primary osteoporosis with severe osteoporotic fracture or extremely low bone mass, and has been reported to increase BMD and to reduce the risk of fractures also in GIOP. Denosumab, an anti receptor activator of nuclear factor-κB ligand, recently approved as a drug for postmenopausal osteoporosis was also effective for GIOP in clinical trials, and would be new candidate to treat GIOP.

Long-term systemic glucocorticoid therapy: Patients’ representations, prescribers’ perceptions, and treatment adherence

IntroductionGlucocorticoids have been used since 1948 for their anti-inflammatory and structural effects in various inflammatory diseases. The optimal use of glucocorticoids remains controversial. Patients may have a number of concerns about the effects of glucocorticoids. Many factors can adversely affect treatment adherence. ObjectivesTo evaluate the main adverse effects reported by patients and physicians, and to assess representations associated with glucocorticoid therapy and the underlying disease, via measurements of treatment adherence, with the goal of optimizing treatment strategies and improving patient information. MethodsFrom December 2011 to May 2012, we conducted two surveys in 125 patients receiving long-term glucocorticoid therapy and followed-up at the rheumatology department of the teaching hospital in Casablanca, Morocco, and in 85 hospital physicians in various specialties, respectively. ResultsMean glucocorticoid therapy duration was 6years, mean maximal prescribed dosage was 44.87mg/d, and 50.4% of the patients had inflammatory joint disease. Adverse neuropsychiatric effects were reported by 70 out of 125 (56%) patients. Weight gain was the adverse effect deemed most bothersome by the physicians, who significantly underestimated the occurrence of neuropsychiatric adverse effects (27% vs 56%, P=0.034). Adherence was poor in 80 out of 125 (64%) patients, and 22 out of 125 (18%) patients reported episodes of treatment discontinuation. ConclusionPrescribers underestimate the frequency of neuropsychiatric adverse effects of long-term systemic glucocorticoid therapy. Regular follow-up visits during treatment, with collection of systemic adverse effects might improve treatment adherence.

Recovery of Adrenal Function after Long-Term Glucocorticoid Therapy for Giant Cell Arteritis: A Cohort Study

ObjectivesGiant cell arteritis (GCA) is a chronic systemic vasculitis of large and medium-sized arteries, for which long-term glucocorticoid (GC) treatment is needed. During GC withdrawal patients can suffer adrenal insufficiency. We sought to determine the time until recovery of adrenal function after long-term GC therapy, and to assess the prevalence and predictors for secondary adrenal insufficiency.Subjects and Design150 patients meeting the ACR criteria for GCA between 1984 and 2012 were analyzed. All received the same GC treatment protocol. The low-dose ACTH stimulation test was repeated annually until adrenal recovery. Biographical, clinical and laboratory data were collected prospectively and compared.ResultsAt the first ACTH test, 74 (49%) patients were non-responders: of these, the mean time until recovery of adrenal function was 14 months (max: 51 months). A normal test response occurred within 36 months in 85% of patients. However, adrenal function never recovered in 5% of patients. GC of >15 mg/day at 6 months, GC of >9.5 mg/day at 12 months, treatment duration of >19 months, a cumulative GC dose of >8.5 g, and a basal cortisol concentration of <386 nmol/L were all statistically associated with a negative response in the first ACTH test (p <0.05).ConclusionAdrenal insufficiency in patients with GCA, treated long-term with GC, was frequent but transitory. Thus, physicians’ vigilance should be increased and an ACTH test should be performed when GC causes the above associated statistical factors.

Growth Hormone and Muscle Strength in Children

When I was asked to write an editorial to comment on the article by Simon et al (1) in this issue of the Journal, I felt it would be a real challenge. The use of GH therapy in children has provoked more discussion in the last few years from a legal, journalistic, economical, and even political point of view than from medical and scientific perspectives. I decided to take the challenge and to comment on the facts as I perceive them. An impact of recombinant human GH (rhGH) on muscle strength is controversial. As physicians, we are essentially warned about rhGH doping in professional and Olympic athletics, with the presumption that it has a beneficial effect on muscle strength. This is despite the fact that there appears to be no evidence that rhGH enhances muscle strength, power, or aerobic capacity in trained adult athletes. However, rhGH does increase modestly anaerobic exercise capacity when administered alone and to a greater extent when combined with testosterone (2). Thus, despite the abuse of rhGH by athletes, there is little support of performance benefit except for an effect on anaerobic exercise capacity (2). In GH-deficient patients, replacement of rhGH improves aerobic exercise capacity, although it remains to be elucidated whether this is due to the direct effect on muscle function or on other factors influencing cardiovascular function, well-being, and motivation. Long-term rhGH replacement in excess of 12 months seems to be required for improved muscle strength to take place in GH-deficient adult subjects (2). It has been reported that 10 years of rhGH replacement therapy in GH-deficient adults increased muscle strength during the first half of the study and then protected partly against the normal decline withage inmusclestrength,resulting inapproximatelynormalized muscle strength after 10 years (3). Even fewerdataareavailable inchildren,with theexception of data gathered from children affected with Prader-Willi syndrome(PWS),araregenetic formofobesitywithhypothalamic involvement that leads to GH deficiency. One group assessed the impact of rhGH therapy begun early in life on the natural history of PWS and compared height, body composition, and strength in similar-age children with PWS naive to rhGH with those treated with hGH for 6 years (4). Motor strength testing included broad jump, agility run, sit-ups, and upper arm strength assessments. The evaluator of motor strength testing was blinded to the treatment status of each child. PWS children treated with rhGH demonstrated greater motor strength (increased standing broad jump 22.9 2.1 vs 14.6 1.9 inches (P .001) and sit-ups 12.4 0.9 vs 7.1 0.7 repetitions in 30 seconds; P .001). Clear trends were seen in the 2 other areas of the testing, including improved agility run and weight-lift repetitions, although these did not reach statistical significance. Thus, thisnonrandomizedstudysuggestedabeneficialeffecton muscle strength in children affected by PWS. However, these few reports on young active adults, on GH-deficient adults, and on children affected by PWS may not be relevant to the chronically ill and less active children included in the study of Simon et al (1). In this study, the authors evaluated the effects of rhGH on muscle strength in children receiving long-term glucocorticoid therapy. Expected effects of growth hormone on height and body composition were assessed and confirmed, but those will not be commented upon here. This was a pilot study, randomized and controlled, with a delayed-start of rhGH for 12 months. rhGH was started after randomization (month 0) or 6 months later (month 6). A total of 30 children with various diagnoses, on glucocorticoid therapy for a chronic disease, startedat least1year earlierwithheight1SDorat2SDscore (SDS) below and bone age 15 years in boys and 13 years in girls. rhGH was administered at a dose of 0.065 mg/kg/d for 6monthsandtheninthedosagemaintainingserumIGF-1levels

Pituitary-Adrenal Function After Prolonged Glucocorticoid Therapy for Systemic Inflammatory Disorders: An Observational Study

Glucocorticoid therapy is being used in a wide variety of systemic disorders. Reference papers, published more than 20 years ago, showed no correlation between adrenal insufficiency risk and dose or duration of glucocorticoid therapy. Our objective was to evaluate the extent to which long-term glucocorticoid therapy damages the pituitary-adrenal axis in patients with systemic inflammatory disorders. We conducted a retrospective observational study from January 2011 to August 2012. This was a monocentric study at the Department of Internal Medicine, Bichat Hospital, Paris-Diderot University, Paris, France. Sixty consecutive patients who were receiving long-term prednisone therapy for systemic inflammatory disorders and in whom discontinuation of glucocorticoid treatment was planned. A short Synacthen test was performed. A bolus of 0.25 mg 1-24-ACTH was injected in the morning, 24 hours after the most recent dose of prednisone. Cortisol was measured at baseline and 60 minutes after Synacthen injection. We assessed frequency and risk estimate of pituitary-adrenal dysfunction. Twenty-nine patients (48.3%) had adrenal insufficiency defined by a plasmatic cortisol <100 nmol/L (n = 13) at baseline (time 0) or <550 nmol/L (n = 16) 60 minutes after Synacthen injection. Cumulative dose (area under the receiver operating characteristic curve = 0.77 [95% confidence interval = 0.62-0.91], P = .007) and exposure (area under the receiver operating characteristic curve 0.80 [95% confidence interval = 0.67-0.93], P = .002) to prednisone were predictive for adrenal insufficiency based on a T0 <100 nmol/L. Prednisone was stopped in 29 of 31 patients (93.5%) showing a normal response to short Synacthen test; none of these patients required hydrocortisone replacement with a mean follow-up of 10 (± 6) months. Adrenal insufficiency is frequent in patients treated with long-term glucocorticoids for systemic inflammatory disorders and is related to duration and cumulative dose of steroids.

Complications de la corticothérapie chez les patients souffrant de maladie de Horton ou de pseudopolyarthrite rhizomélique

Giant cell arteritis and polymyalgia rheumatica are common reasons for prescribing long-term glucocorticoid therapy. Glucocorticoids efficacy in these patients is rapid and undeniable, but it is often overshadowed by adverse events, appearing more or less early during treatment course. These adverse events are usually minor but some of them may be life threatening. Because of the absence of randomized, controlled trials comparing glucocorticoids to placebo in this indication and in this aged population, it is difficult to precise the role of corticosteroids in the occurrence of some complications that can also be precipitated by the disease itself (e.g., vascular complications) or related to aging. In this context, analysis of the crude morbidity and mortality can help in anticipating the potential problems that these patients will encounter. In addition, the long duration of glucocorticoid exposure should prompt physicians to be particularly vigilant regarding some adverse events that are minimally symptomatic on the short term but have a major long-term impact.

Long-Term Inflammation and Glucocorticoid Therapy Impair Skeletal Modeling During Growth in Childhood Crohn Disease

Glucocorticoids and inflammation inhibit bone formation; however, the impact on skeletal modeling is unknown. The objectives of the study were to examine changes in bone mineral density (BMD) and cortical structure after Crohn disease (CD) diagnosis and identify associations with growth, glucocorticoids, and disease activity. This was a prospective cohort study among 76 CD participants, aged 5-21 years. Tibia quantitative computed tomography trabecular BMD and cortical dimensions were obtained at diagnosis and 6 and 12 and a median of 42 months later; 51 completed the final visit. Sex, race, and age-specific Z-scores were generated for outcomes based on more than 650 reference participants, and cortical dimension Z-scores were further adjusted for tibia length. Generalized estimating equations were used to model changes in Z-scores. Disease activity improved over the study interval (P < .001). Trabecular BMD Z-scores improved over the first 6 months; increases were associated with improved disease activity (P < .001), younger age (P = .005), and increases in vitamin D levels (P = .02). Greater increases in tibia length were associated with greater increases in cortical area Z-scores (P < .001). Greater glucocorticoid doses and disease activity were significantly associated with failure to accrue cortical area and were more pronounced with greater linear growth (interaction P < .05). Mean (±SD) trabecular BMD (-1.0 ± 1.21) and cortical area (-0.57 ± 1.10) Z-scores at the final visit were significantly reduced. CD was associated with persistent deficits in trabecular BMD, although younger participants demonstrated a greater potential for recovery. In addition, greater linear growth was associated with a greater recovery of cortical dimensions, especially among participants with less glucocorticoid exposure and inflammation. These data suggest that younger age and concurrent growth provide a window of opportunity for skeletal recovery.

Long-term safety, efficacy, and patient acceptability of teriparatide in the management of glucocorticoid-induced osteoporosis

Glucocorticoids are commonly prescribed medications to treat multiple diseases across many medical specialties. One of the most common yet largely unappreciated side effect of glucocorticoid use is increased risk of fracture. Many different therapies are indicated to prevent and treat this condition; many guidelines exist that suggest appropriate use of both glucocorticoids and the medications approved to prevent this common side effect of glucocorticoid therapy. Nevertheless, 30%–50% of patients on long-term glucocorticoid therapy sustain a fracture. Teriparatide, recombinant human parathyroid hormone (1–34), is a daily self-injectable therapy for 24 months approved for use in patients taking long-term glucocorticoids. Teriparatide has been shown to increase bone mineral density and reduce vertebral fracture risk in glucocorticoid-treated patients. Glucocorticoids have many adverse effects on bone that teriparatide has been shown to prevent or negate. Given the fact that preventive therapy for glucocorticoid-induced osteoporosis is often not prescribed, one wonders whether a daily self-injectable therapy for this condition would be prescribed by physicians and accepted by patients. This article reviews the epidemiology, pathophysiology, treatment, guidelines, and persistence data (when available) for patients with glucocorticoid-induced osteoporosis treated with teriparatide.

Effects of Recombinant Human Growth Hormone for 1 Year on Body Composition and Muscle Strength in Children on Long-Term Steroid Therapy: Randomized Controlled, Delayed-Start Study

Recombinant human GH (rhGH) improves growth and body composition in glucocorticoid-treated children. Its effects on muscle strength are poorly evaluated. Our objective was to evaluate rhGH effects on muscle strength in children receiving long-term glucocorticoid therapy; effects on height SD score (SDS) and body composition were assessed also. A randomized, controlled, delayed-start study of rhGH for 12 months was started after randomization (baseline) or 6 months later (M6). Patients included 30 children with various diagnoses. rhGH was administered at 0.065 mg/kg/d for 6 months and then in the dosage maintaining serum IGF-I levels below +2 SDS for chronological age. The primary criterion was the between-group difference in composite index of muscle strength (CIMS) change at M6. Secondary criteria included between-group differences in CIMS SDS(height), lean mass (LM), thigh muscle area (MA), and height SDS changes at M6; these parameters were also assessed in the overall population after 1 year of rhGH therapy. At M6, rhGH therapy did not significantly affect changes in CIMS or CIMS SDS(height) (+17.6% vs +7.5% and +0.14 ± 0.38 vs +0.11 ± 0.62, respectively); the rhGH-treated group had significantly larger changes in height SDS (+0.2 [0.3] vs -0.2 [0.3]; P = 0.003), LM (+7.3% [+3.7%; +21.6%] vs 0% [-4.7%; +3.2%]; P = 0.002), and MA (+8.8% [+5%; +15.6%] vs. -0.6% [-6.3%; +7.7%]; P = 0.01) compared with the untreated group. After 1 year of rhGH, height SDS, LM, and MA increased significantly, CIMS increased by 24.7% (+5.8%; +34.2%), and CIMS SDS(height) remained within the normal range. rhGH increased height, LM, and MA. However, muscle strength did not improve significantly.