Is there a potential dual effect of denosumab for treatment of osteoporosis and sarcopenia?

BACKGROUND: The prevalence of sarcopenia with osteoporosis results in a higher risk of falling and fractures. It was noted that patients who had completed their planned 5-year denosumab therapy course as treatment for these conditions started to sustain falls. PURPOSE: To assess (a) whether denosumab has a unique dual effect on both bone and muscle in comparison to other anti-resorptive agents and (b) its effectiveness in the follow-up period post-treatment completion compared to other anti-resorptive agents. METHOD: One hundred thirty-five patients diagnosed to have postmenopausal/senile osteoporosis and who were prescribed denosumab were compared to a control group of 272 patients stratified into 2 subgroups - 136 prescribed alendronate and 136 prescribed zoledronate. All patients were assessed for: BMD (DXA), falls risk (FRAS), fracture risk (FRAX), and sarcopenia measures. All were re-assessed after 5 years of denosumab/alendronate therapy and 3 years of zoledronate and 1 year after stopping the osteoporosis therapy. RESULTS: No significant baseline demographic differences between the 3 groups. On completion of the 5-year denosumab therapy, there was significant decrease in falls risk (P = 0.001) and significant improvements in all sarcopenia measures (P = 0.01). One-year post-discontinuation of denosumab, a significant worsening of both falls risk and sarcopenia measures (P = 0.01) noticed. CONCLUSION: Denosumab displayed positive impact and significant improvements in BMD and sarcopenia measures. It also enhanced multidirectional agility as depicted by Timed Up and Go (TUG). Collectively, this would explain the reduction of falls risk which got worse on stopping the medication. Key points • The coexistence of osteoporosis and sarcopenia has been recently considered in some groups as a syndrome termed 'osteosarcopenia'. • Bone and muscle closely interact with each other not only anatomically, but also at the chemical and metabolic levels. • Denosumab displayed positive impact and significant improvements in all sarcopenia measures, and enhanced multidirectional agility with consequent reduction in falls risk. • Denosumab can be considered as a first osteoporosis therapeutic option in this group of patients presenting with osteosarcopenia manifestations.

Effective control of polymyalgia rheumatica with tocilizumab.

Despite their disadvantages, glucocorticoids (GCs) remain a mainstay of therapy for polymyalgia rheumatica (PMR). Second-line antirheumatic and immune-modulatory drugs are not infrequently required because of disease relapses during GC tapering and GC adverse effects. Therapy with methotrexate or with an anti-tumor necrosis factor drug showed modest efficacy in this situation. Tocilizumab (TCZ) is an anti-interleukin 6 receptor antibody that is being recently studied in the treatment of PMR patients who are intolerant or refractory to GCs, especially after failure of a second-line agent. We report a case of PMR in which GCs were stopped because of adverse effects despite good response. The condition responded to neither methotrexate nor etanercept. Treatment with TCZ has led to significant improvement of the patient's clinical and biochemical PMR activity parameters, and she was kept in a solid remission for 1 year without any TCZ-related adverse effects. Tocilizumab is a promising drug in the management of PMR. Further studies are required to clearly define the indications and duration of TCZ therapy in the management of PMR.

Central pontine myelinolysis in the hyperosmolar hyperglycaemic state.

OBJECTIVE: To report a rare association of central pontine myelinolysis (CPM) with hyperosmolar hyperglycaemic state (HHS). CLINICAL PRESENTATION AND INTERVENTION: A diabetic female presented with HHS and prolonged severe hypernatraemia. The metabolic derangement was adequately treated with proper correction of both hyperglycaemia and hypernatraemia. Lack of improvement in the presenting confusional state and the development of a fresh neurological deterioration led to the suspicion of CPM that was confirmed with magnetic resonance imaging. She fully recovered after 4 weeks with no specific medical treatment. CONCLUSION: This case report showed that osmotic demyelination was linked to hypernatraemia and that CPM could result from severe hypernatraemia of HHS.

Atypical clinical manifestations of graves' disease: an analysis in depth.

Over the past few decades, there has been an increase in the number of reports about newly recognized (atypical or unusual) manifestations of Graves' disease (GD), that are related to various body systems. One of these manifestations is sometimes the main presenting feature of GD. Some of the atypical manifestations are specifically related to GD, while others are also similarly seen in patients with other forms of hyperthyroidism. Lack of knowledge of the association between these findings and GD may lead to delay in diagnosis, misdiagnosis, or unnecessary investigations. The atypical clinical presentations of GD include anemia, vomiting, jaundice, and right heart failure. There is one type of anemia that is not explained by any of the known etiological factors and responds well to hyperthyroidism treatment. This type of anemia resembles anemia of chronic disease and may be termed GD anemia. Other forms of anemia that are associated with GD include pernicious anemia, iron deficiency anemia of celiac disease, and autoimmune hemolytic anemia. Vomiting has been reported as a presenting feature of Graves' disease. Some cases had the typical findings of hyperthyroidism initially masked, and the vomiting did not improve until hyperthyroidism has been detected and treated. Hyperthyroidism may present with jaundice, and on the other hand, deep jaundice may develop with the onset of overt hyperthyroidism in previously compensated chronic liver disease patients. Pulmonary hypertension is reported to be associated with GD and to respond to its treatment. GD-related pulmonary hypertension may be so severe to produce isolated right-sided heart failure that is occasionally found as the presenting manifestation of GD.

Hypothermia with pneumonia: a rare presentation of brucellosis.

OBJECTIVE: To report a very rare form of brucellosis presenting with hypothermia and pneumonia. CLINICAL PRESENTATION AND INTERVENTION: A 41-year-old male shepherd presented with a depressed level of consciousness. Clinically, his rectal temperature was 29.5°C, and he was cold, apathetic, hyporeflexic, and hypotensive, with atrial fibrillation. He had clinical and radiological evidence of bilateral bronchopneumonia. Blood culture and serologic testing were positive for Brucella melitensis. The patient recovered completely after proper management of the hypothermia and treatment of the brucellosis with antibiotics (doxycycline 100 mg orally twice daily for 6 weeks and streptomycin 1 g i.m. daily for 21 days). CONCLUSION: This case shows that brucellosis should be considered in the differential diagnosis of septicemic patients presenting with hypothermia.

Anticoagulation for cerebral venous thrombosis with subarachnoid hemorrhage: a case report.

OBJECTIVES: To report the success of anticoagulation (AC) treatment in a case of cerebral venous thrombosis (CVT) with subarachnoid hemorrhage (SAH) in view of the limited evidence seen in the literature supporting such a treatment option. CLINICAL PRESENTATION AND INTERVENTION: A 38-year-old lady with CVT and SAH presented 12 h after the onset of symptoms. AC with low-molecular-weight heparin was started 4 days later, when the repeated brain CT showed regression of the SAH. Heparin was changed to warfarin, and she was asymptomatic over a 12-month follow-up period. DISCUSSION: In a limited number of small studies, AC has been found to be beneficial for cases of CVT with hemorrhagic complications. The proper time to start AC in such cases was not clearly defined, and a delay of 4-33 days was observed after the onset of symptoms. In cases of spontaneous intracranial hemorrhage (ICH) in general, active bleeding is usually confined to the first 6 h, and chances of hematoma enlargement are higher in the first 24 h. On the other hand, it has been advised to rule out a coincidental vascular malformation and to radiologically confirm regression (or at least non-progression) of the ICH before starting AC. CONCLUSION: AC for cases of CVT may remain beneficial in the presence of SAH. The time to start AC for CVT with hemorrhagic complications is unclear; however, AC was successful when given 4 days after the onset of symptoms in our case. It may be wise to repeat CT after at least 24 h from the onset of symptoms (to confirm regression or at least non-progression of the ICH) before starting AC. It may also be prudent to perform magnetic resonance angiography, or digital subtraction angiography to rule out a coincidental intracranial aneurysm before AC.

Pulmonary hypertension responding to hyperthyroidism treatment.

Pulmonary hypertension in adults with hyperthyroidism is increasingly being reported. Although the mechanism is uncertain, the reversal of pulmonary hypertension following restoration to an euthyroid state supports a causal relationship. This case report is of a 43-year-old woman who presented with Graves disease and right ventricular failure. Echocardiography showed severe pulmonary hypertension, moderate to severe tricuspid regurgitation, normal left heart function and a negative bubble contrast study. Carbimazole therapy was instituted along with diuretics and captopril. The patient was followed for a period of 14 months. Clinical and biochemical euthyroidism was attained after 4 months of treatment. Resolution of right ventricular failure and normalization of pulmonary artery pressure occurred 11 and 14 months after initiation of therapy, respectively. Investigating thyroid status in patients with pulmonary hypertension is recommended. In patients with hyperthyroidism and (otherwise unexplained) pulmonary hypertension, restoration of euthyroidism may cure right ventricular failure and restore normal pulmonary artery pressure.