I am not sure how to translate this study in children with acute pain to our patients with various pain syndromes. Growing pains usually respond very nicely to NSAIDs, perhaps reflecting the acuity of this problem. Patients with hypermobility and pain and those with patello-femoral syndrome often have more chronic pain. Do these patients parallel those in the cohort with soft tissue injury, who were more resistant to pain relief, or the group with fracture, who received reasonable pain relief—or are they different still? My take-home message for hypermobile/patello-femoral pain: try pushing ibuprofen higher than my usual 10 mg/kg and add on a narcotic analgesic (at least for short periods) and get those kids to physical therapy. I think I will save acetaminophen for treatment of low-grade fever.
The Role of DKK-1 in RA
By Maripat Corr, MD
Diarra D, Stolina M, Polzer K, et al. Dickkopf-1 is a master regulator of joint remodeling. Nat Med. 2007;13(2):156-163.
Abstract
Degenerative and inflammatory joint diseases lead to destruction of the joint architecture. Whereas degenerative osteoarthritis results in the formation of new bone, rheumatoid arthritis leads to bone resorption. The molecular basis of these different patterns of joint disease is unknown. By inhibiting Dickkopf-1 (DKK-1), a regulatory molecule of the wingless (Wnt) pathway, we were able to reverse the bone-destructive pattern of a mouse model of rheumatoid arthritis to the bone-forming pattern of osteoarthritis. In this way, no overall bone erosion resulted, although bony nodules, so-called osteophytes, did form. We identified tumor necrosis factor–a (TNF-a) as a key inducer of DKK-1 in the mouse inflammatory arthritis model and in human rheumatoid arthritis. These results suggest that the Wnt pathway is a key regulator of joint remodeling.
Commentary
Inflammatory arthritis is coupled with structural changes in the underlying bone. These bony changes can be either erosive, as seen in rheumatoid arthritis (RA), or proliferative, as exemplified by ankylosing spondylitis. Hence, soluble regulators of bone remodeling have been a topic of intensive investigative interest. Recently, the Wnt signaling pathway has been identified as a key pathway in maintaining adult bone mass and bone turnover.
Wnt proteins are extracellular ligands which bind to the G-protein-coupled seven-transmembrane domain frizzled receptors and the low-density lipoprotein receptor-related protein 5 and 6 (LRP5/6) coreceptors. Receptor ligation triggers a cascade of events that stabilizes beta-catenin, and enables its nuclear translocation and subsequent activity as a transcriptional cofactor.1 Gain of function polymorphisms in the LRP 5 coreceptor results in elevated bone mass and bony proliferation, and loss of function variants result in the osteoporosis pseudoglioma syndrome.2,3 The DKK family of soluble Wnt antagonists binds to LRP and another receptor called Kremen. (See Figure 1) Diarra et al. have identified one of these molecules, DKK-1, as a key modulator of bone remodeling disorders. In addition its potential as a therapeutic target, serum levels of his protein might be a surrigate biomarker for disease-associated bone remodeling.