Bone remodeling is achieved through the coupled activities of osteoclasts and osteoblasts that are controlled by many locally generated secreted factors, including WNT5A. While previous studies have demonstrated that osteoblast‐derived WNT5A promotes osteoclastogenesis, the function of osteoclast‐derived WNT5A on bone remodeling has remained unexplored. We examined the effects of osteoclast‐derived WNT5A on bone homeostasis by utilizing the Cathepsin K‐Cre (Ctsk‐Cre) mouse to conditionally delete Wnt5a in mature osteoclasts. These mice exhibited reduced trabecular and cortical bone. The low bone–mass phenotype was driven by decreased bone formation, not osteoclast‐mediated bone resorption, as osteoclast number and serum CTX marker were unchanged. Furthermore, molecular analysis of osteoclast‐ and osteoblast‐derived WNT5A identified a serine‐phosphorylated WNT5A that is unique to RANKL‐treated macrophages mimicking osteoclasts. This study suggests a new paradigm in which WNT5A has opposing effects on bone remodeling that are dependent on the cell of origin, an effect that may result from cell type–specific differential posttranslational modifications of WNT5A.

Background Droxidopa is an oral treatment for the stepwise treatment of neurogenic orthostatic hypotension from autonomic dysfunction. It has been shown to be useful predominantly with neurogenic orthostatic hypotension secondary to Parkinson’s disease, but only a few cases have documented its usefulness in patients with neurogenic orthostatic hypotension due to amyloidosis, which is often severe and refractory. In addition, only one source in the literature reports the concomitant use of midodrine and droxidopa for such patients. Finally, we argue that droxidopa seems to have a protective effect against episodes of reflex bradycardia, which is not previously reported. Case presentation A 64-year-old white man was admitted for 1 year of worsening syncopal episodes, diarrhea, failure to thrive, heart failure, and neuropathy. Medical emergencies were called five times on the overhead hospital intercom over a 4-day period in the beginning of his admission due to severe hypotension and bradycardia. He was eventually diagnosed as having amyloid light-chain amyloidosis and myeloma. After starting droxidopa, both his systolic blood pressure and reflex bradycardia improved, and no more medical emergency events were called during the remaining 30 days of admission. He felt much better subjectively and was able to sit upright and engage in physical therapy. Conclusions We show that droxidopa is effective when used with midodrine to treat refractory neurogenic orthostatic hypotension in patients with amyloidosis. There are very few cases reporting the use of droxidopa in amyloidosis, with only one study that uses droxidopa and midodrine concomitantly. In addition, our patient’s reflex bradycardia improved drastically after starting droxidopa, which we believe is mediated by increased systemic norepinephrine. There were no side effects to droxidopa, and the benefits lasted well beyond the reported duration of 1–2 weeks that was noted to be a limitation in some studies.

No abstract

Context: Lesser metatarsophalangeal (MTP) instability is a common condition that can become debilitating and require surgery. Evidence Acquisition: An extensive literature review was performed through MEDLINE and Google Scholar for publications relating to the etiology, diagnosis, and treatment of lesser MTP instability using the keywords metatarsophalangeal instability, athlete, forefoot pain, and metatarsalgia from database inception to 2019. Study Design: Clinical review. Level of Evidence: Level 4. Results: Lesser MTP instability is a common condition, especially in the active and aging populations. It is frequently misdiagnosed, causing delays in treatment that allow for progressive pain and deformity, which prevents an active lifestyle. Fortunately, MTP instability can be diagnosed easily with the drawer test. Magnetic resonance imaging is helpful when still in doubt. Conservative treatment entails joint immobilization and gradual return to play with taping and offloading metatarsal pads. Conclusion: Lesser MTP instability is a common diagnosis. Its early detection and conservative treatment can help the patient regain their previous level of activity and avoid surgery.

No abstract