Denosumab (Amgen, Thousand Oaks, California, USA) is a new bone antiresorptive agent used in patients with osteoporosis or metastatic cancer to the bones. As with the bisphosphonates that are used as antiresorptive medications, denosumab has been associated with osteonecrosis of the jaws (ONJ). Over the past two years there has been an increase in the literature describing ONJ in patients receiving agents such as denosumab. Due to promising study results that demonstrate the effectiveness of denosumab in avoiding skeletal complications related to osteoporosis and metastatic bone disease, more patients will receive denosumab in the future. It is reported that this has the potential to become a comparable challenge to bisphosphonate related osteonecrosis of the jaws (BRONJ) for clinicians. This article describes the management of two patients that developed ONJ while receiving denosumab, reviews the incidence of ONJ associated with denosumab, and contrasts the pharmacokinetics of denosumab and the bisphosphonates. The importance of avoiding interventional dental treatment until denosumab has been withdrawn for six months cannot be overstated.Keywords: Bisphosphonates, bisphosphonate related osteonecrosis of the jaws, denosumab, denosumab associated osteonecrosis of the jaws, necrosis of the jaws.Abbreviations and acronyms: BP = bisphosphonate; BRONJ = bisphosphonate related osteonecrosis of the jaws; DONJ = denosumab associated osteonecrosis of the jaws; FDA = US Food and Drug Administration; ONJ = osteonecrosis of the jaws; OPG = osteoprotegerin; PET = positron emission tomography; RANK = receptor activator of nuclear factor kappa; RANKL = receptor activator of nuclear factor kappa-B ligand.

Purpose of Review Rapid advances in imaging of the prostate have facilitated the development of focal therapy and provided a non-invasive method of estimating tumour volume. Focal therapy relies on an accurate estimate of tumour volume for patient selection and treatment planning so that the optimal energy dose can be delivered to the target area(s) of the prostate while minimising toxicity to surrounding structures. This review provides an overview of different imaging modalities which may be used to optimise tumour volume assessment and critically evaluates the published evidence for each modality. Recent Findings Multi-parametric MRI (mp-MRI) has become the standard tool for patient selection and guiding focal therapy treatment. The current evidence suggests that mp-MRI may underestimate tumour volume, although there is a large variability in results. There remain significant methodological challenges associated with pathological processing and accurate co-registration of histopathological data with mp-MRI. Advances in different ultrasound modalities are showing promise but there has been limited research into tumour volume estimation. The role of PSMA PET/CT is still evolving and further investigation is needed to establish if this is a viable technique for prostate tumour volumetric assessment. Summary mp-MRI provides the necessary tumour volume information required for selecting patients and guiding focal therapy treatment. The potential for underestimation of tumour volume should be taken into account and an additional margin applied to ensure adequate treatment coverage. At present, there are no other viable image-based alternatives although advances in new technologies may refine volume estimations in the future.

Background Light chain proximal tubulopathy (LCPT) is a rare form of paraprotein-related disease, occurring in two main histopathological forms; crystalline and non-crystalline. The clinicopathological features, treatment strategies and outcomes, especially of the non-crystalline form, are not well described. Methods Single-centre retrospective case series of 12 LCPT patients, 5 crystalline and 7 non-crystalline, between 2005-2021. Observations Median age was 69.5 years (range, 47-80). 10 patients presented with CKD and significant proteinuria (median eGFR of 43.5 ml/min/1.73m2; uPCR 328 mg/mmol). Only 6 patients had known haematological disease at the time of renal biopsy. Multiple myeloma (MM) was diagnosed in 7 cases and MGRS in 5. A clone was detected in all cases combining serum/urine electrophoresis and free LC assays. Crystalline and non-crystalline variants had similar clinical presentations. For the non-crystalline variant, a diagnosis was reached based on combination of CKD without other cause, haematological work-up, LC restriction on IF and abnormalities on EM. Nine of 12 patients received clone-directed treatment. Patients who achieved haematological response (including all non-crystalline LCPT) had improved renal outcomes over a median follow-up of 79 months. Conclusions The non-crystalline variant may go unrecognised because of its subtle histopathological features and requires EM to distinguish it from “excessive LC resorption without tubular injury”. Clone-directed treatment with good haematological response improves renal outcomes in both variants but limited data exist in MGRS. Multi-centre prospective studies are needed to better define the clinico-pathological characteristics associated with poor outcomes and optimize treatment strategies in patients with MGRS.