Normal bone growth is achieved by a balance between bone formation by osteoblasts and bone resorption (breakdown of bone matrix) by osteoclasts. In<unk> , the number of osteoclasts may be reduced, normal, or increased. Most importantly, osteoclast dysfunction mediates the pathogenesis of this disease.<unk>  is caused by underlying mutations that interfere with the acidification of the osteoclast resorption pit, for example due to a deficiency of the carbonic anhydrase enzyme encoded by the CA2 gene. Carbonic anhydrase is required by osteoclasts for proton production. Without this enzyme hydrogen ion pumping is inhibited and bone resorption by osteoclasts is defective, as an acidic environment is needed to dissociate calcium hydroxyapatite from the bone matrix. As bone resorption fails while bone formation continues, excessive bone is formed. Mutations in at least nine genes cause the various types of<unk> . Mutations in the CLCN7 gene are responsible for about 75 percent of cases of autosomal dominant<unk> , 10 to 15 percent of cases of autosomal recessive<unk> , and all known cases of intermediate autosomal<unk> . TCIRG1 gene mutations cause about 50 percent of cases of autosomal recessive<unk> . Mutations in other genes are less common causes of autosomal dominant and autosomal recessive forms of the disorder. The X-linked type of<unk> , OL-EDA-ID, results from mutations in the IKBKG gene. In about 30 percent of all cases of<unk> , the cause of the condition is unknown. The genes associated with<unk>  are involved in the formation, development, and function of specialized cells called osteoclasts. These cells break down bone tissue during bone remodeling, a normal process in which old bone is removed and new bone is created to replace it. Bones are constantly being remodeled, and the process is carefully controlled to ensure that bones stay strong and healthy. Mutations in any of the genes associated with<unk>  lead to abnormal or missing osteoclasts. Without functional osteoclasts, old bone is not broken down as new bone is formed. As a result, bones throughout the skeleton become unusually dense. The bones are also structurally abnormal, making them prone to fracture. These problems with bone remodeling underlie all of the major features of<unk> .Protein TNFSF 11(RANKL)
Osteopetrosis
Avascular necrosis
Leri pleonosteosis
Osteochondrosis
Osteitis fibrosa cystica
Osteofibrous dysplasia
Osteoma
Osteopoikilosis