Even in trials with as many as 125 children, no causal link has been found between bisphosphonates and decreased fracture rates; placebo controlled trials were also unable to prove that they brought about increased strength, motor control or lower pain levels.Bisphosphonates are not as effective at increasing the bone mineral density of adults. Nutritional supplements
OI is a genetic disorder and is not caused by insufficient intake of any vitamin or mineral; supplementation cannot cure OI. With that said, people with OI tend to be severely deficient in vitamin D at much higher rates than the general population, and the cause of this is not well understood. The severity of the deficiency and the likelihood of its occurrence is thought to be related to severity of OI. Vitamin D supplementation may be recommended, at least until levels of 25(OH)D3 in blood return to normal. Below normal levels of vitamin D are also concerning as they may decrease the benefit of bisphosphanates. Surgery
A surgery of any type inherently carries more risks when done on a patient who has (especially moderate to severe) OI. Skeletal deformities and dentinogenesis imperfecta may hinder access to the airway. : 333  Use of, and weaning off of, mechanical ventilation is also more challenging to carry out on patients with OI. : 333  During the procedure itself or the healing process, defective OI collagen may lead to bleeding diatheses.
A tophus (Latin: "stone", plural tophi) is a deposit of monosodium urate crystals, in people with longstanding high levels of uric acid in the blood, a condition known as hyperuricemia. Tophi are pathognomonic for the disease gout. Most people with tophi have had previous attacks of acute arthritis, eventually leading to the formation of tophi. Chronic tophaceous gout is known as Harrison Syndrome.Tophi form in the joints, cartilage, bones, and other places throughout the body. Sometimes, tophi break through the skin and appear as white or yellowish-white, chalky nodules. Without treatment, tophi may develop on average about ten years after the onset of gout, although their first appearance can range from three to forty-two years. The development of gouty tophi can also limit joint function and cause bone destruction, leading to noticeable disabilities, especially when gout cannot successfully be treated. When uric acid levels and gout symptoms cannot be controlled with standard gout medicines that decrease the production of uric acid (e.g., allopurinol, febuxostat) or increase uric acid elimination from the body through the kidneys (e.g., probenecid), this can be referred to as refractory chronic gout (RCG). They are more apt to appear early in the course of the disease in people who are older. Although less common, tophi can also form in the kidneys and nasal cartilage. Pathophysiology
It appears that monosodium urate crystals trigger a distinct physiological NETosis pathway that coats them in DNA. These coated crystals then persist in tissues as a foreign body granuloma constituting gouty tophus.