Osteoporosis is a global public health problem, with fractures contributing to significant morbidity and mortality. Although post-menopausal osteoporosis is most common, up to 30% of post-menopausal women, >50% of premenopausal women, and between 50-80% of men have secondary osteoporosis. Exclusion of secondary causes is important as treatment of such patients often commences by treating the underlying condition. These are varied but often neglected, ranging from endocrine to chronic inflammatory and genetic conditions. General screening is recommended for all patients with osteoporosis with advanced investigations reserved for premenopausal women and men aged <50 years, for older patients in whom classical risk factors for osteoporosis are absent, and for all patients with the lowest bone mass (Z-score ≤-2). The response of secondary osteoporosis to conventional anti-osteoporosis therapy may be inadequate if the underlying condition is unrecognized and untreated. Bone densitometry, using dual energy x-ray absorptiometry (DXA), may underestimate fracture risk in some chronic diseases including glucocorticoid-induced osteoporosis, type 2 diabetes and obesity, and may overestimate fracture risk in others (e.g. Turner syndrome). FRAX ® and TBS may provide additional information regarding fracture risk in secondary osteoporosis, but their use is limited to adults aged ≥40 years and ≥50 years, respectively. In additional FRAX ® requires adjustment in some chronic conditions e.g. glucocorticoid dose, type 2 diabetes and HIV. In most conditions, evidence for antiresorptive or anabolic therapy is limited to increases in bone mass. Current osteoporosis management guidelines also neglect secondary osteoporosis and these existing evidence gaps are discussed.
Immune checkpoint inhibitors offer patients with advanced melanoma substantial improvements in survival. Unlike chemotherapy, immune checkpoint inhibitors such as ipilimumab and pembrolizumab cause unique immune-related adverse events (irAEs), including the development of endocrinopathies. We report a case of a man aged 60 years who developed diabetic ketoacidosis (DKA) following the use of pembrolizumab for the treatment of metastatic melanoma. He received four cycles of ipilimumab, before proceeding to pembrolizumab. Five weeks after initiating pembrolizumab, he presented in DKA with a pH of 7.0, bicarbonate of 7 mmol/L, blood glucose of 27 mmol/L and serum ketones of 5.9 mmol/L. Antibodies to glutamic acid decarboxylase (anti-GAD) and Islet antigen 2 (IA-2) were negative and C-peptide was low at 57 pmol/L (300-2350 pmol/L). There was no personal or family history of autoimmune conditions. Standard immunosuppression for irAEs was started using prednisolone in an attempt to salvage β cell function but was unsuccessful. To the best of our knowledge, this is the first reported attempt at reversing pembrolizumab-induced type 1 diabetes using glucocorticoids.
A lower TBS, suggestive of increased microarchitectural damage, was associated with type 1 DM, markers of higher bone turnover, and prevalent fracture. These data support the need for prospective studies to evaluate whether TBS inclusion improves fracture prediction in patients with ESKD.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.