American Bone Health has closed. However, on October 1, 2023, we joined forces with the Bone Health and Osteoporosis Foundation (BHOF) so that BHOF could continue offering all of the important programs and services created by American Bone Health. Please visit www.bonehealthandosteoporosis.
There are many diseases that involve the bones. Osteoporosis might be the most common, affecting more than 10 million Americans. Some 44 million more Americans have low bone density that increases their risk of broken bones.
American Bone Health wants to call attention to some other diseases that are far less common.
These are the rare bone diseases. They are genetic, sometimes inherited by a child from a parent. They affect the metabolism of the bones. They can appear at birth or even earlier. Their effects can range from mild to devastating.
By definition, a “rare disease” in the U.S. affects fewer than 200,000 people. The National Organization for Rare Disorders counts 1,200 rare diseases in its database. The low numbers of people affected means these diseases can be difficult to research. There is a lack of published data. Treatments are not well known or widely available. There is a lack of support and resources.
This Rare Bone Disease Encyclopedia is meant to provide some basic information for people researching these diseases. The entries below discuss disease descriptions, symptoms, prevalence, and treatment. Perhaps most important, they point users to advocacy groups that specialize in specific diseases. These organizations can be a lifeline for people affected by these diseases and their families.
Here are some other general resources for rare diseases:
Description: Hypophosphatasia (HPP) is a genetic disorder that affects the development of teeth and bones. It impairs the mineralization of the teeth and bones. This makes the bones soft and more likely to fracture. It also can cause premature tooth loss and other dental problems. The signs and symptoms of hypophosphatasia vary widely. The disease can occur anywhere from before birth to adulthood.
Prevalence: About 500–600 people in the U.S. are known to have hypophosphatasia. More people with HPP maybe be unrecognized or misdiagnosed. In its most severe, fatal form, HPP occurs in 1-in-100,000 births. A milder, potentially much more common form of HPP occurs in at least 4-in-1,000 adults.
Symptoms: There are six different types of hypophosphatasia. They have varying symptoms depending on what age the disease develops. The most severe symptoms occur at the youngest stages. Adult HPP symptoms are usually categorized as “adult rickets,” including soft bones, frequent fractures, and chronic joint and muscle pain. Adult-onset HPP may appear similar to osteoporosis, including low bone mineral density and sometimes stress fractures in the feet or thigh bones.
Diagnosis: Hypophosphatasia is usually diagnosed upon identifying symptoms and reviewing patient history, which likely has many complications. It is also identified using clinical examinations, imaging, and different laboratory tests. People with HPP have low levels of an enzyme called alkaline phosphatase (ALP), but testing for ALP alone is not enough to diagnose HPP. People who routinely have a total alkaline phosphatase level at or below 40 may have HPP and should have a vitamin B6 level measured when they are not taking any supplemental B-vitamins, including a multivitamin. The combination of a low total alkaline phosphatase level and an elevated vitamin B6 level pretty much diagnoses a patient as likely having HPP. This is important because patients with HPP lack the gene for bone-specific alkaline phosphatase, which is released by bone-forming osteoblasts in order to break down inorganic pyrophosphate (which among other actions inhibits bone mineralization). Because the very effective osteoporosis drugs known as bisphosphonates are analogs of inorganic pyrophosphate, no patient with HPP should ever be treated with a bisphosphonate. Genetic testing for a mutation to the ALPL gene also can help diagnose HPP but is not always needed if a patient has a low total alkaline phosphatase, a very low bone-specific alkaline phosphatase, and an elevated vitamin B level.
Treatment: Treatment focuses on managing symptoms such as hypercalcemia and chronic pain. A human recombinant enzyme replacement therapy called asfotase alfa (Strensiq) is approved to treat bone problems in people with pediatric-onset HPP. People with HPP should not be treated with bisphosphonates, which are often used to treat osteoporosis. Although anabolic agents used to treat osteoporosis, such as Forteo (teriparatide) and Tymlos (abaloparatide), can be used in patients with HPP.
To learn more, visit: Soft Bones
References:
American Bone Health presents the BoneSense Speaker Series replay of the live webinar “Adult Hypophosphatasia: An Uncommon Bone Disease Hiding in Plain Sight”. Hear from a physician who treats patients with adult hypophosphatasia and a patient advocate who was diagnosed with adult HPP in 2018.
Description: Gaucher disease is a rare genetic disorder that children inherit from their parents. People with Gaucher disease are missing an enzyme that breaks down fatty substances called lipids. Dangerous amounts of fatty substances accumulate in the body, especially the bone marrow, liver and spleen. This accumulation causes problems and symptoms with the organs.
Prevalence: About 6,000 people the U.S. have been diagnosed with Gaucher disease. It is the second-most common type of lysosomal storage disorder.
Symptoms: There are three different types of Gaucher disease that are categorized by the age when it develops. The most common symptoms are easy bruising, chronic fatigue, enlarged liver or spleen, bone pain due to lack of blood supply to bones, degeneration and deformity of affected bones, and weakening of bones. When it occurs at a younger age, it can present symptoms such as mental deterioration, inability to coordinate movements, brief muscle spasms, or difficulty moving eyes side to side.
Diagnosis: Can be considered in patients who have unexplained bruising or anemia. It can be confirmed through clinical evaluation, specialized tests that measure acid beta-glucosidase activity in white blood cells, or DNA tests that look for the causal gene.
Treatment: Depending on the type of Gaucher disease, there are different treatment options and possibilities. For types 1 and 3, the most effective treatment is enzyme replacement therapy, which has been proven to reduce most symptoms and can be useful for all types. Type 2, which occurs in newborns and infants, is likely untreatable due to patients’ age and severity of symptoms. There are also medicines that have been approved by the FDA and are proven to be effective at lessening symptoms. Miglustat (Zavesca®) and eliglustat (Cerdelga®) appear to interfere with the production of fatty substances that build up in people with Gaucher disease.
To learn more, visit: Gaucher Community Alliance
References:
Description: A disorder in which chondrogenic lesions form on the long bones, such as the femur, tibia and humerus. It is an inherited genetic disorder caused by mutations to tumor-suppressing genes.
Prevalence: About 2,000 cases in the United States.
Symptoms: Prominent bumps on the bones, especially the long bones; painful snapping of muscle or tendon over the outgrowths, short stature, limbs of different lengths, knees or ankles turned outward, deformed forearm, loss of forearm rotation.
Diagnosis: Nonmobile masses in the limbs can be detected during a clinical exam. Range of motion of the nearby joints should be assessed as well.
Treatment: The most effective and common treatment is through a surgical removal of the lesions and rehabilitation to ensure the best recovery.
To learn more visit: MHE and Me
References:
Description: Also known as “brittle bone disease,” it is a group of genetic disorders that affect connective tissue, namely Type 1 collagen, which comprises the bone matrix. Babies are born with it. The disease causes fragile bones that can break easily. Severity varies from person to person. Four main types account for 85-90% of cases. Type I being the most common and mild, causing just a few fractures in a person’s lifetime. Type II is the most severe, usually causing death within a few weeks of birth. The most common type diagnosed in adults is Type IV, which is the most variable form, with symptoms ranging from moderately severe to so mild that making a diagnosis may be difficult.
Prevalence: Between 20,000 and 50,000 people in the U.S. It appears in 1-in-20,000 live births in the U.S.
Symptoms: Type and severity vary. Some people never have a fracture, others have a few, and some have many, even hundreds in a lifetime. In Type I, most people suffer from multiple fractures that occur during childhood and continue through puberty before declining. Patients with Type I tend to have blueish discoloration in the white of their eyes, triangular faces, below average height, and can develop scoliosis. Type II is the most severe and affects mostly infants causing low birth weights, complications at birth, malformed bones, and underdeveloped respiratory system and upper chest.
Diagnosis: Based on clinical evaluation and looking at patient medical and family records. Genetic testing is used to detect the specific gene causing the mutation. Clinical tests can diagnose osteogenesis imperfecta before birth.
Treatment: Usually focused on individual symptoms with focus on nutrition and exercise to promote bone health and growth. Bisphosphonate medicines are used to improve bone density and normalize bone turnover and to prevent fractures in children suffering from more severe symptoms. In severe cases, surgery is performed to remove pressure on the skull and spine connection or to insert rods into the longer leg bones to increase support. Sometimes, anabolic medicines such as Forteo (teriparatide) or Tymlos (abaloparatide) are used in patients with osteogenesis imperfecta Type IV.
To learn more, visit: OI Foundation
References:
Description: Osteomalacia is caused by a serious vitamin D deficiency that causes the bones to soften. In children, it is known as rickets. As the individual grows, the bones can become bowed.
Prevalence: Hard to determine. Most patients have no symptoms. The condition tends to develop with age.
Symptoms: Symptoms may not arise in the early stages. When they do, patients suffer bone pain and weakened muscles. Pain is usually worst at night. Areas most commonly affected are the lower back, pelvis, hips, legs, and ribs. May result in fractures and can appear similar to osteoporosis.
Diagnosis: Usually comes through blood or urine testing to check vitamin D levels. A low vitamin D level along with elevated alkaline phosphatase and elevated parathyroid hormone (PTH) is consistent with a diagnosis of osteomalacia. Bone biopsy also can be done but generally is not needed.
Treatment: Taking vitamin D and calcium supplements and treating disorders that might cause the condition.
To learn more visit: Genetic and Rare Diseases Information Center
References:
Description: A rare bone disease caused by abnormal phosphate and vitamin D metabolism. This disease tends to be misdiagnosed or undiagnosed. Also known as TIO or osteogenic osteomalacia.
Prevalence: Unknown. About 500 cases have been reported in scientific literature.
https://www.nature.com/articles/nrdp201744
Symptoms: Bone pain, muscle weakness, height loss, and multiple fractures.
Diagnosis: Chronically low phosphate levels along with the above symptoms. Locating the offending tumor can be difficult as it is often very small and can be located anywhere in the body.
Treatment: Surgical removal of the tumor is the only definitive treatment. When the tumor cannot be located or when complete removal is not possible, medical treatment with phosphate salts or active vitamin D is necessary. A monoclonal antibody called KRN23 or burosumab (marketed under the brand name Crysvita®) is approved for treating TIO.
To learn more, visit: National Organization for Rare Disorders (NORD).
References:
Description: X-linked hypophosphatemia (XLH) is a genetic disorder characterized by low levels of phosphorus in the blood. When a person has XLH, their kidneys cannot properly manage vitamin D and phosphorus. This causes symptoms and disorders that affect the bones and teeth.
Prevalence: Affects about 1-in-20,000 people worldwide. It is the most common form of genetic rickets in the United States.
Symptoms: Abnormal development of bones and teeth. Many people with XLH develop rickets, which causes knock-knees or bowed legs. People with XLH also can have waddling gait, short stature, spontaneous tooth abscesses, and bone and muscle pains.
Diagnosis: Review of symptoms can lead to a diagnosis, which is confirmed through genetic testing. Symptoms sometimes are apparent before a child begins to walk. However, most cases display only limited symptoms, and many people are not tested. XLH often goes undiagnosed and sometimes is misdiagnosed as a vitamin D deficiency.
Treatment: Early diagnosis is important for effective treatment. A monoclonal antibody called burosumab (Crysvita®) can reduce phosphate-wasting and improve vitamin D metabolism in children and adults.
To learn more, visit:
References:
Description: A rare genetic disorder that causes the bones to become overly dense due to reduced activity of bone-resorbing osteoclasts. Patients with osteopetrosis usually have very high bone mineral density as measured by DXA. Abnormal growth causes the bones to have defective architecture. They become brittle and fracture easily. These large, misshapen bones lead to other health problems, as well. There are three different types that vary based on how the disease was inherited. The most common of the three genetic types is the autosomal dominant form, which means it is inherited from only one parent; this form has generally mild symptoms that usually present in late childhood to adulthood. People with this form often have X-rays that show osteosclerosis (overly dense bones), and may have low-trauma fractures from brittle, dense bones in adulthood.
Prevalence: About 1,250 people in the U.S. have osteopetrosis.
Symptoms: Bone fractures and low blood cell production. Changes to the size and shape of the skull can press on the nerves, causing hearing and vision loss, congested nasal passages, and dental problems.
Diagnosis: Clinical evaluation, detailed patient history, and specialized tests such as X-rays can be used to diagnose osteopetrosis. Genetic testing can be used to determine the exact mutation in around 90% of cases, making it easier to find treatment. The presence of very positive T-scores (high BMD on DXA) along with an elevated acid phosphatase, CK-BB and often an increased bone-specific alkaline phosphatase supports the diagnosis of osteopetrosis.
Treatment: The only proven cure for osteopetrosis is for autosomal recessive malignant infantile osteopetrosis. This uses stem cell transplantation to try and reverse the affects. For other types it is best to keep up with a healthy diet that includes high levels of calcium and vitamin D.
To learn more, visit: The Osteopetrosis Society
Reference: https://medlineplus.gov/genetics/condition/osteopetrosis/
Description: One of the most common bone growth abnormalities, it is the No. 1 cause of dwarfism. In about 80% of people with achondroplasia, it occurs spontaneously due to a mutation in the father’s sperm. The rest inherit the mutation from a parent with the condition. Affected individuals tend to have an abnormally large head, short arms and legs, and short height. Their faces appear small relative to their heads. Examples of people with achondroplasia are the actor Peter Dinklage (“Cyrano,” “Game of Thrones”), stunt performer Jason “Wee Man” Acuña (“Jackass”), as well as most of the actors who played the Munchkins in “The Wizard of Oz.”
Prevalence: It occurs in about 1-in-20,000 or 30,000 live births.
Symptoms: Growth defects that present themselves as short stature, short arms, and a protrusive stomach and butt. The back is prominently swayed. Achondroplasia does not affect intelligence.
Diagnosis: Based on a check of the symptoms and confirmed using X-rays during infancy. Genetic testing can be used to confirm a diagnosis and determine where the mutation came from.
Treatment: Voxzogo® (vosoritide) is indicated to modestly increase growth in children with achondroplasia. Other treatments focus on reducing symptoms depending on severity of an individual’s condition. If there is swelling around the brainstem and spinal cord, then a consultation with a neurosurgeon will be necessary. Other treatments are currently being researched are are in clinical development.
To learn more, visit:
References:
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