UK clinical guideline for the prevention and treatment of osteoporosis

The National Osteoporosis Guideline Group (NOGG) has revised the UK guideline for the assessment and management of osteoporosis and the prevention of fragility fractures in postmenopausal women, and men age 50 years and older. Accredited by NICE, this guideline is relevant for all healthcare professionals involved in osteoporosis management. INTRODUCTION The UK National Osteoporosis Guideline Group (NOGG) first produced a guideline on the prevention and treatment of osteoporosis in 2008, with updates in 2013 and 2017. This paper presents a major update of the guideline, the scope of which is to review the assessment and management of osteoporosis and the prevention of fragility fractures in postmenopausal women, and men age 50 years and older. METHODS Where available, systematic reviews, meta-analyses and randomised controlled trials were used to provide the evidence base. Conclusions and recommendations were systematically graded according to the strength of the available evidence. RESULTS Review of the evidence and recommendations are provided for the diagnosis of osteoporosis, fracture-risk assessment and intervention thresholds, management of vertebral fractures, non-pharmacological and pharmacological treatments, including duration and monitoring of anti-resorptive therapy, glucocorticoid-induced osteoporosis, and models of care for fracture prevention. Recommendations are made for training; service leads and commissioners of healthcare; and for review criteria for audit and quality improvement. CONCLUSION The guideline, which has received accreditation from the National Institute of Health and Care Excellence (NICE), provides a comprehensive overview of the assessment and management of osteoporosis for all healthcare professionals involved in its management. This position paper has been endorsed by the International Osteoporosis Foundation and by the European Society for the Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases

Review: New perspectives in the management of primary hyperparathyroidism

Primary hyperparathyroidism (PHPT) is a biochemical syndrome caused by the inappropriate or unregulated overproduction of parathyroid hormone, leading to hypercalcaemia. It was previously considered a relatively rare disorder, with clinical manifestations dominated by renal and/or bone disease. However, in modern times the diagnosis is most frequently recognized coincidentally on biochemical testing in patients evaluated for unrelated complaints. Parathyroidectomy is the only curative treatment for PHPT, with improved outcomes in symptomatic patients following this procedure. However, surgical intervention in patients with no clear clinical features remains controversial. The National Institutes for Health (NIH) have developed consensus guidelines giving specific indications for when surgery is recommended in patients with asymptomatic PHPT. This article examines the impact of treatment on asymptomatic PHPT, focusing on bone disease, neurocognitive function, quality of life, cardiovascular disease and mortality. Medical treatment options, including bisphosphonates and cinacalcet, are also discussed

Mild primary hyperparathyroidism-to treat or not to treat?

INTRODUCTION The presentation of primary hyperparathyroidism (PHPT) has shifted from a disease characterized by renal and skeletal complications to a mild or asymptomatic condition. Modern imaging allows localization of a surgical target in the majority of cases. SOURCES OF DATA Data were collected from literature searches of online databases including PUBMED, MEDLINE and Cochrane. A narrative review was performed. AREAS OF AGREEMENT Parathyroidectomy is the only therapy with curative potential with good outcomes and low risk of complications in experienced hands. Current guidelines advocate that surgery is offered in all symptomatic cases and in those who meet criteria depending on age, serum calcium concentration, skeletal and renal parameters. A structured monitoring approach should be offered to those who do not undergo surgery. AREAS OF CONTROVERSY Thresholds for intervention to improve skeletal and renal outcomes are debatable. In addition, controversy persists over the benefit of surgery for non-skeletal/renal outcomes. GROWING POINTS The role of medical management of PHPT using agents such as bisphosphonates, denosumab and cinacalcet are discussed. AREAS TIMELY FOR DEVELOPING RESEARCH In summary, further data on the natural history and effects of treatment of mild and asymptomatic PHPT are required to determine thresholds for surgery. In particular, further investigations of non-skeletal and non-renal parameters, such as neurocognitive quality of life and cardiovascular disease are required. Data on normocalcaemic PHPT are lacking. Large-scale randomized controlled trials would be welcome in these areas, however in view of the cost implications a more pragmatic approach may be to develop collaborative multi-centre registries

Epidemiology and financial burden of adult chronic hypoparathyroidism

Chronic hypoparathyroidism is characterized by low serum calcium, increased serum phosphorus, and inappropriately low or decreased serum parathyroid hormone. This rare disorder is associated with a variety of complications. The prevalence, incidence, mortality, financial burden, and epidemiology of complications of this disorder are not well understood. This narrative review summarizes current information on the epidemiology and complications of chronic hypoparathyroidism. The reported prevalence of chronic hypoparathyroidism ranges from 6.4–37/100,000, and the incidence is reported to be 0.8–2.3/100,000/year. Mortality is not increased in studies from Denmark or South Korea but was increased in studies from Scotland and Sweden. The financial burden of this disorder is substantial because of increased health care resource utilization in two studies but not well quantitated. Recognized complications include hypercalciuria, nephrocalcinosis, kidney stones, and chronic kidney disease; low bone turnover and possibly upper extremity fractures; cardiac and vascular calcifications; basal ganglia calcifications, cataracts, infections, neuropsychiatric complications, and difficulties with pregnancy. This review concludes that chronic hypoparathyroidism is a rare disorder associated with significant morbidity that may not increase overall mortality but is associated with a substantial financial burden

Expression of 11β-hydroxysteroid dehydrogenase enzymes in human osteosarcoma:potential role in pathogenesis and as targets for treatments

Osteosarcoma (OS) is a primary malignant tumour of bone occurring predominantly in children and young adults. Despite chemotherapy, relapse is common and mortality remains high. Non-transformed osteoblasts are highly sensitive to glucocorticoids, which reduce proliferation and induce apoptosis. Previously, we observed that OS cells, but not normal osteoblasts, express 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). This enzyme inactivates cortisol (active) to cortisone (inactive) and expression of 11β-HSD2 renders OS cells resistant to glucocorticoids. By contrast, the related enzyme 11β-HSD1 converts cortisone to cortisol and reduces OS cell proliferation in vitro. Some synthetic glucocorticoids (e.g. dehydrodexamethasone (DHD), inactive counterpart of dexamethasone (DEX)) have been reported to be activated by 11β-HSD2. We therefore investigated expression and enzymatic activity of 11β-HSD isozymes in human OS tissue, determined whether 11β-HSD expression has prognostic value in the response to therapy, and evaluated the potential use of synthetic glucocorticoids to selectively target OS cells. OS samples expressed both 11β-HSD1 and 11β-HSD2. 11β-HSD1 expression in pretreatment biopsy specimens positively correlated with primary tumour size. Expression and activity of 11β-HSD1 in post-treatment biopsies were unrelated to the degree of tumour necrosis following chemotherapy. However, high 11β-HSD2 expression in post-treatment biopsies correlated with a poor response to therapy. OS cells that expressed 11β-HSD2 inactivated endogenous glucocorticoids; but these cells were also able to generate DEX from DHD. These results suggest that OS treatment response is related to 11β-HSD2 enzyme expression. Furthermore, OS cells expressing this enzyme could be targeted by treatment with synthetic glucocorticoids that are selectively reactivated by the enzyme.</jats:p