SummaryThyroid fine-needle biopsy (FNB) is a simple, reliable, inexpensive and generally safe diagnostic procedure in the management of thyroid nodules. Post-FNB local pain and minor haematomas are the most common complications, while serious complications seem to be rare. Given that use of FNB minimizes unnecessary surgery and subsequent operative morbidity and mortality as well as the fact that the majority of FNB complications resolve spontaneously, the overall safety of FNB is not questioned. However, awareness of the potential complications and careful estimation of the risk-benefit ratio in an individual basis may further decrease the low morbidity of FNB. In this systematic review we tried to collect and summarize all reported clinical complications following diagnostic thyroid FNB, aiming to make physicians aware of possible complications and to provide preventive measures to avoid them.

We aimed to study the clinical and imaging characteristics of patients sustaining vertebral fractures after denosumab discontinuation. For this purpose, we conducted a computerized advanced literature search that identified 13 published cases, and we additionally included another 11 new cases from our centers. Twenty-four postmenopausal women with vertebral fracture(s) after denosumab discontinuation, experiencing 112 fractures in total, were analyzed. The mean number of fractures per patient was 4.7. The most commonly affected vertebrae were T12 and L1. All fractures occurred 8 to 16 months after the last denosumab injection. Eighty-three percent of the patients were treatment naïve, whereas 33% had prevalent vertebral fractures. Five (23%) patients were on concurrent aromatase inhibitor treatment. When patients were divided according to treatment duration with an arbitrary cut-off of 2 years, those with ≤2 years of denosumab treatment had fewer fractures compared with those with >2 years (mean ± SEM fractures 3.2 ± 0.7 versus 5.2 ± 1.4, p = 0.055). Vertebroplasty was used in 5 patients, resulting in additional clinical vertebral fractures in all cases. We conclude that vertebral fracture(s) after denosumab discontinuation are in the majority of patients multiples, and they occur a few months after the effect of the last dose is depleted. Therefore, patients should not delay or omit denosumab doses. Fractures are typically osteoporotic, located at the lower thoracic and the upper lumbar spine. Vertebroplasty is an unsuccessful treatment strategy for such patients. © 2017 American Society for Bone and Mineral Research.

Context Denosumab discontinuation is characterized by an increase in bone turnover overriding pre-treatment status, a rapid bone loss in the majority and multiple vertebral fractures (VFx) in some patients. Methods A working group of the European Calcified Tissue Society (ECTS) performed an updated systematic review of existing literature on changes of bone turnover, bone mineral density (BMD), and fracture risk after denosumab discontinuation and provided advice on management based on expert opinion. Results Important risk factors for multiple VFx following denosumab cessation are prevalent VFx, longer duration off therapy, greater gain in hip BMD during therapy, and greater loss of hip BMD after therapy according to a retrospective analysis of the FREEDOM Extension Study. Case series indicate that prior bisphosphonate therapy mitigates the biochemical rebound phenomenon after denosumab discontinuation, but it is uncertain whether this attenuation prevents BMD loss and fractures. Current evidence indicates partial efficacy of subsequent antiresorptive treatment with results seemingly dependent on duration of denosumab treatment. Conclusions A careful assessment of indications to start denosumab treatment is advised, especially for younger patients. A case for long-term treatment with denosumab can be made for patients at high fracture risk already on denosumab treatment given the favorable efficacy and safety profile. In case of denosumab discontinuation, alternative antiresorptive treatment should be initiated 6 months after the final denosumab injection. Assessment of bone turnover markers may help define the optimal regimen, pending results of ongoing RCTs. Patients having sustained VFx should be offered prompt treatment to reduce high bone turnover.

Previous antiresorptive (AR) treatment may influence the response to teriparatide. We examined BMD response and safety in a subgroup of 503 postmenopausal women with osteoporosis who received teriparatide for 24 mo. Patients were divided into three groups based on their prior AR treatment: treatmentnaïve (n ‫ס‬ 84); pretreated with no evidence of inadequate treatment response (n ‫ס‬ 134); and pretreated showing an inadequate response to AR treatment (n ‫ס‬ 285), which was predefined based on the occurrence of fractures, persistent low BMD, and/or significant BMD loss while on therapy. Changes in BMD from baseline were analyzed using mixed model repeated measures. Lumbar spine BMD increased significantly from baseline at 6, 12, 18, and 24 mo in all three groups. The mean gain in spine BMD over 24 mo was greater in the treatment-naïve group (0.095 g/cm 2 ; 13.1%) than in the AR pretreated (0.074 g/cm 2 ; 10.2%; p < 0.005) and inadequate AR responder (0.071 g/cm 2 ; 9.8%; p < 0.001) groups. The corresponding increases in total hip BMD were 3.8%, 2.3%, and 2.3%, respectively. Early decreases in hip BMD in the inadequate AR responder group were reversed by 18 mo of treatment. Increases in BMD between 18 and 24 mo were highly significant. Nausea (13.3%) and arthralgia (11.7%) were the most commonly reported adverse events. Asymptomatic hypercalcemia was reported in 5.0% of patients. Teriparatide treatment for 24 mo is associated with a significant increase in BMD in patients with and without previous AR use. Prior AR treatment modestly blunted the BMD response to teriparatide. Safety was consistent with current prescribing label information.

In healthy, young individuals, circulating irisin displays a day-night rhythm, is correlated with lean body mass, and increases acutely after exercise.