Management of glucocorticoid-induced osteoporosis

Messina, Osvaldo Daniel; Vidal, Luis; Vidal, Maritza; Bultink, Irene E. M.; Raterman, Hennie G.; Lems, W.F.

doi:10.1007/s40520-021-01823-0

Cited by 26 publications

(12 citation statements)

References 86 publications

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“…By interfering with several important signaling pathways, glucocorticoids cause the differentiation of precursor cells into adipocytes, ultimately decreasing the number of osteoblasts ( 3 ). Glucocorticoids also cause increased production of inhibitors of Wnt signaling, such as sclerostin, leading to a reduction in bone formation ( 4 , 5 ). Moreover, high doses of corticosteroids can lead to osteoblast apoptosis ( 6 ).…”

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confidence: 99%

Effect of AZD4017, a Selective 11β-HSD1 Inhibitor, on Bone Turnover Markers in Postmenopausal Osteopenia

Abbas

Schini

Ainsworth

et al. 2022

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context The causative link between circulating glucocorticoid excess and osteoporosis is well-established. The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) increases local cortisol production, is expressed in human osteoblasts and its activity increases with age. We hypothesized that local 11β-HSD1 might mediate an age-related decrease in bone formation and that selective 11β-HSD1 inhibition may enhance bone formation. Methods A twin-centre phase II randomized, double-blind, placebo-controlled trial of 90 days’ treatment with AZD4017 (a selective 11β-HSD1 inhibitor) was conducted. 55 post-menopausal women with osteopenia were recruited. Participants received 400mg twice daily of oral AZD4017 compared to matched placebo over 90 days. The primary outcome measure was the impact on the bone formation marker, osteocalcin. Secondary objectives included correlation with 11β-HSD1 activity. Results At 90 days the levels of osteocalcin did not differ between the treatment groups, active [mean 22.3 (SD 8.6) ng/ml, n=22] and placebo [21.7 (SD 9.2) ng/ml, n=24], with an adjusted for baseline treatment effect of 0.95 (95% CI: -2.69, 4.60). The results from the urinary [THF+alloTHF]/THE ratio (index of 11β-HSD1 activity) and the urinary cortisol/cortisone ratio (index of 11β-HSD2 activity), confirmed a >90% inhibition of 11β-HSD1 but no change in activity of 11β-HSD2. Conclusion This trial demonstrates that AZD 4017 selectively inhibits 11β-HSD1 activity in vivo in a safe and reversible manner. Following treatment for 90 days there is no effect on bone formation, indicating that the relative impairment of bone mineral density in post-menopausal women is not mediated by local intracellular production of cortisol, under normal physiological concentrations.

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confidence: 99%

Effect of AZD4017, a Selective 11β-HSD1 Inhibitor, on Bone Turnover Markers in Postmenopausal Osteopenia

Abbas

Schini

Ainsworth

et al. 2022

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…In COPD for example, shorter glucocorticoid pulses are nowadays preferred over longer courses, due to similar effectiveness and the possibility of less cumulative toxicity ( 49 ). Glucocorticoid stewardship in general involves prescribing the lowest effective dose for the shortest possible time ( 50 ).…”

Section: Resultsmentioning

confidence: 99%

Prevention and Treatment of Glucocorticoid-Induced Osteoporosis in Adults: Consensus Recommendations From the Belgian Bone Club

et al. 2022

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Glucocorticoids are effective immunomodulatory drugs used for many inflammatory disorders as well as in transplant recipients. However, both iatrogenic and endogenous glucocorticoid excess are also associated with several side effects including an increased risk of osteoporosis and fractures. Glucocorticoid-induced osteoporosis (GIOP) is a common secondary cause of osteoporosis in adults. Despite availability of clear evidence and international guidelines for the prevention of GIOP, a large treatment gap remains. In this narrative review, the Belgian Bone Club (BBC) updates its 2006 consensus recommendations for the prevention and treatment of GIOP in adults. The pathophysiology of GIOP is multifactorial. The BBC strongly advises non-pharmacological measures including physical exercise, smoking cessation and avoidance of alcohol abuse in all adults at risk for osteoporosis. Glucocorticoids are associated with impaired intestinal calcium absorption; the BBC therefore strongly recommend sufficient calcium intake and avoidance of vitamin D deficiency. We recommend assessment of fracture risk, taking age, sex, menopausal status, prior fractures, glucocorticoid dose, other clinical risk factors and bone mineral density into account. Placebo-controlled randomized controlled trials have demonstrated the efficacy of alendronate, risedronate, zoledronate, denosumab and teriparatide in GIOP. We suggest monitoring by dual-energy X-ray absorptiometry (DXA) and vertebral fracture identification one year after glucocorticoid initiation. The trabecular bone score might be considered during DXA monitoring. Extended femur scans might be considered at the time of DXA imaging in glucocorticoid users on long-term (≥ 3 years) antiresorptive therapy. Bone turnover markers may be considered for monitoring treatment with anti-resorptive or osteoanabolic drugs in GIOP. Although the pathophysiology of solid organ and hematopoietic stem cell transplantation-induced osteoporosis extends beyond GIOP alone, the BBC recommends similar evaluation, prevention, treatment and follow-up principles in these patients. Efforts to close the treatment gap in GIOP and implement available effective fracture prevention strategies into clinical practice in primary, secondary and tertiary care are urgently needed.

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“…Adapted from Refs. [10,[26][27][28][29][30][31][32]. AI aromatase inhibitor, PostMW postmenopausal women, PreMW, premenopausal women, GnRH Gonadotropin-Releasing Hormone, GC glucocorti-coids, ART antiretroviral treatment, PLWH people living with HIV, TDF tenofovir disoproxil fumarate, PrEP HIV pre-exposure prophylaxis and macrophages help create a microenvironment that promotes the recruitment of osteoclasts [45].…”

Section: Change Of Spine Bmd At One Year (%)mentioning

confidence: 99%

Osteoporosis and HIV Infection

Biver

2022

Calcif Tissue Int

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Life expectancy of people living with HIV (PLWH) is now close to that of the HIV-uninfected population. As a result, age-related comorbidities, including osteoporosis, are increasing in PLWH. This narrative review describes the epidemiology of bone fragility in PLWH, changes of bone features over the course of HIV infection and their determinants, as well as the available evidence regarding the management of osteoporosis in PLWH. The risk of fracture is higher and increases about 10 years earlier compared to the general population. The classical risk factors of bone fragility are very widespread and are major determinants of bone health in this population. The majority of bone loss occurs during virus replication and during immune reconstitution at antiretroviral therapies (ART) initiation, which both increase osteoclast activity. Abnormalities in bone formation and mineralization have also been shown in histomorphometric studies in untreated PLWH. Measurement of bone mineral density (BMD) is the first line tool for assessing fracture risk in postmenopausal women, men above 50 years, and other HIV-infected patients with clinical risk factors for osteoporosis. FRAX underestimates fracture probability in PLWH. In case of indication for anti-osteoporotic drug, bisphosphonates remain the reference option. Calcium and vitamin D supplementation should be considered as ART initiation, since it may attenuate bone loss at this stage. Bone-protective ART regimens improve BMD compared to other regimens, but to a lesser extent than bisphosphonate, and without available data on their influence on the incidence of fracture.

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Management of glucocorticoid-induced osteoporosis

Cited by 26 publications

References 86 publications

Effect of AZD4017, a Selective 11β-HSD1 Inhibitor, on Bone Turnover Markers in Postmenopausal Osteopenia

Effect of AZD4017, a Selective 11β-HSD1 Inhibitor, on Bone Turnover Markers in Postmenopausal Osteopenia

Prevention and Treatment of Glucocorticoid-Induced Osteoporosis in Adults: Consensus Recommendations From the Belgian Bone Club

Osteoporosis and HIV Infection

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