Related Terms

  • Autosomal dominant disorders, autosomal recessive disorders, blue sclera, brittle bone disease, COL1A1, COL1A2, collagen, connective tissue disorders, CRTAP, LEPRE1, OI, P3H1, prolyl 3-hydroxylase 1.


  • Osteogenesis imperfecta or OI (meaning “imperfect bone formation”) is a group of inherited disorders that affects the bones and connective tissues. People with this condition are born with a reduced bone mass, which results in fragile bones that break easily.
  • There are at least eight forms of OI that are distinguished by the severity of the symptoms. Milder cases sometimes go unnoticed until adulthood and may involve only a few bone fractures. In severe cases, the bones are extremely fragile and may fracture frequently, even with no or little apparent cause.
  • Collagen is the major protein of the body’s connective tissue. It is part of the framework around which bones are formed. Most types of OI (about 85%) are caused by a mutation in the gene that produces type 1 collagen. There are many different mutations that can affect this gene. The severity of OI depends on the specific gene mutation, which can cause the body to make either too little or low-quality type 1 collagen. It is estimated that 20,000-50,000 people in the United States have OI.
  • People with OI may have blue sclera, meaning that the whites of the eyes have a blue tint. They may also have a short stature, hearing loss, restricted physical abilities, breathing problems, and weak teeth. Despite these symptoms, most people with OI live relatively normal lives.

Risk Factors

  • Because osteogenesis imperfecta (OI) is inherited, the only known risk factor is a family history of the disorder. Evidence that OI preferentially affects any particular gender, ethnicity, or age group, is lacking in the available literature.


  • General: Osteogenesis imperfecta (OI) is usually caused by genetic defects that affect the body’s ability to make strong bones. In the majority of OI cases, a person has too little type I collagen or type I collagen that is of poor quality due to a mutation in one of the genes that encode for the protein that makes type I collagen.
  • Mutations: Mutations in the COL1A1 and COL1A2 genes are responsible for most cases of OI. These genes provide instructions for making proteins that are used to assemble type I collagen. This type of collagen is the most abundant protein in bone, skin, and other connective tissues. These mutations are responsible for most cases of types II, III, and IV OI. These genetic changes reduce the amount of type I collagen produced in the body, which causes bones to be brittle and to break easily.
  • Mutations in the CRTAP and LEPRE1 genes are responsible for rare, often severe cases of OI. Cases caused by CRTAP mutations are classified as type VII. Cases caused by LEPRE1 mutations are classified as type VIII. The proteins produced from these genes work together to process collagen into its mature form. These mutations weaken connective tissues, leading to severe bone abnormalities and problems with growth.
  • In some individuals, no mutations are detectable. In cases of OI without identified mutations in the COL1A1, COL1A2, CRTAP, or LEPRE1 genes, the cause of the disorder is unknown. These cases include types V and VI. Scientists are working to identify additional genes that may be responsible for these conditions. In other cases of OI, there are mutations in a cartilage-related protein called 3-prolyl-hydroxylase.
  • Autosomal dominant inheritance: Most cases of OI are caused by an autosomal dominant genetic defect. Each gene has two variations, called alleles. One allele is inherited from each parent. For diseases that are inherited as autosomal dominant traits, only one mutated allele is necessary for the child to have OI. A parent with this type of OI has a 50% chance of passing on the disorder to each child. Types of OI than can be inherited in an autosomal dominant manner are types I, II, III, and IV.
  • Autosomal recessive inheritance: Approximately 10% to 15% of cases of OI are the result of an autosomal recessive mutation. In this case, an affected child receives a copy of the mutated gene from both parents. Most often, parents of a child with an autosomal recessive disorder are not affected but possess, or are carriers of, one copy of the mutated gene. If both parents are carriers, there is a 25% chance of having an affected child with each pregnancy. Types of OI that can be inherited in an autosomal recessive manner include types VII and VIII. Some unusual cases of type III are autosomal recessive.
  • Random occurrence: While most cases of OI are inherited from a parent, some are the result of spontaneous or new genetic mutations that occur early in fetal development. These cases tend to be severe, and occur within individuals with no family history of the disorder. The collagen-encoding genes that are mutated in these cases are usually COL1A1 or COL1A2.

Signs and Symptoms

  • Symptoms of osteogenesis imperfecta (OI) vary greatly from person to person, even among people with the same type of the disorder. All affected individuals have weak bones that break easily. They are usually below average height.
  • Other symptoms may include a blue tint to the whites of the eyes (blue sclera), early hearing loss, loose joints, bowed arms and legs, scoliosis (curved spine), lung problems, flat feet, and poorly developed teeth. These symptoms are caused by the defective formation of bone and connective tissue.
  • The most severe forms of OI, particularly type II, can include an abnormally small, fragile rib cage and underdeveloped lungs. Affected infants may die from breathing problems.


  • Complications are based on the type of osteogenesis imperfecta (OI) present. They are often directly related to problems with weak bones and improperly formed collagen. Casting of broken bones should be limited since further bone loss may occur when a part of the body is not used for a period of time. This is called atrophy or a wasting away of a part of the body.
  • Hearing loss is common in type I and type III because the bones of the ear that are necessary for hearing become fragile. Heart failure may occur in type II, possibly due to not enough oxygen getting to the heart. Other complications may include respiratory problems and pneumonias due to chest wall deformities, spinal cord or brain stem problems, and respiratory failure.


  • General: It may be possible to diagnose osteogenesis imperfecta (OI) based solely on symptoms. OI is usually suspected in children whose bones break with very little force. A physical examination may show that the whites of the eyes (sclera) have a blue tint.
  • Collagen analysis: Collagen analysis from a skin sample may confirm a clinical diagnosis. The collagen biopsy test looks for mutations in the COL1A1, COL1A2, CRTAP, and LEPRE1 genes.
  • Genetic tests: DNA sequencing from a blood sample may confirm a clinical diagnosis. A positive type I collagen genetic test confirms the diagnosis of autosomal dominant OI, but a negative result does not rule out OI. When a type I collagen mutation is not found, other DNA tests are used to check for other types of OI. Due to the fact that so many different mutations can cause OI and that many mutations have not been identified, some forms cannot be diagnosed with a genetic test.
  • Prenatal diagnosis: Severe forms can sometimes be diagnosed prenatally (or while the fetus develops in the womb). If there is a family history of OI, chorionic villus sampling or amniocentesis may be done during pregnancy to determine if the baby has mutations that could cause the condition. In some cases, an ultrasound can identify bone abnormalities in an unborn baby at 14-18 weeks.


  • General: There is no known cure for osteogenesis imperfecta (OI). Treatment aims to prevent or control the symptoms, maximize mobility, and maintain or increase bone mass and muscle strength. Casting of broken bones should be limited since further bone loss may occur when a part of the body is not used for a period of time. This is called atrophy or a wasting away of a part of the body. A social worker or psychologist can help young people adapt to life with OI.
  • Activity: Swimming and water therapy may be helpful to patients with OI. Walking, if possible, is also recommended. People with OI should consult with their physician and/or physical therapist to discuss appropriate and safe exercise.
  • Assistive devices: The use of wheelchairs, braces, and other mobility aids is common among people with more severe types of OI.
  • Diet: OI patients also benefit from maintaining a healthy weight and eating a nutritious diet. OI patients should avoid smoking and excessive alcohol and caffeine consumption, which can decrease bone strength.
  • Drugs: Bisphosphonates are the best drug therapy available to treat OI. These are drugs that have been used to treat osteoporosis and have been proven to be very valuable in the treatment of OI symptoms, particularly in children. They work by inhibiting the breakdown of bone and its resorption by the body. Benefits of bisphosphonate treatment include decreased pain, lower fracture incidence, better mobility, and increased strength and bone density. Among the various bisphosphonates, pamidronate (brand name Aredia®) given intravenously (IV) has been shown to reduce bone pain and increase bone mass and density. However, the optimal treatment dose and the long-term effects of pamidronate treatment are not known. Treatment with bisphosphonates during growth may be reserved for patients who have severe or life-threatening symptoms.
  • Growth hormone treatment and an injected drug called teriparatide, are being evaluated. These treatments can stimulate bone growth. People with OI should avoid taking steroid medications, which can decrease bone strength.
  • Gene-based therapies: Gene-based therapies for OI patients are currently being studied. A new approach has been developed to replace mutated genes using stem cells and DNA. It is experimental and limited by the number of gene mutations.
  • Surgery:
    Reconstructive surgery may be needed to correct deformities such as bowed legs or spinal problems. A surgical procedure called “rodding” is frequently used. Rodding involves inserting metal rods through the length of the long bones to strengthen them, prevent and correct deformities, and to reduce the risk of fracture.

Integrative Therapies

: Currently, there is a lack of scientific data on the use of integrative therapies for the treatment or prevention of osteogenesis imperfecta (OI). The integrative therapies listed below should be used only under the supervision of a qualified healthcare provider and should not be used in replacement of other proven therapies.


Strong scientific evidence

  • Calcium
    : Calcium is the nutrient consistently found to be the most important for attaining peak bone mass and preventing osteoporosis. Adequate vitamin D intake is required for optimal calcium absorption. Adequate calcium and vitamin D are deemed essential for the prevention of osteoporosis in general, including postmenopausal osteoporosis. Although calcium and vitamin D alone are not recommended as the sole treatment for osteoporosis, they are necessary additions to pharmaceutical treatments. The majority of clinical trials investigating the efficacy of pharmaceutical treatments for osteoporosis have investigated these agents in combination with calcium and vitamin D. So, although calcium alone is unlikely to have an effect on the rate of bone loss following menopause, osteoporosis cannot be treated in the absence of calcium. Treatment of postmenopausal osteoporosis should only be done under the supervision of a qualified healthcare professional.

  • Avoid if allergic or hypersensitive to calcium or lactose. High doses taken by mouth may cause kidney stones. Avoid with hypercalcemia (high levels of calcium in the blood), hypercalciuria (high levels of calcium in urine), hyperparathyroidism (high levels of parathyroid hormone), bone tumors, digitalis toxicity, ventricular fibrillation (ventricles of the heart contract in unsynchronized rhythm), kidney stones, kidney disease, or sarcoidosis (inflammation of lymph nodes and various other tissues). Calcium supplements made from dolomite, oyster shells, or bone meal may contain unacceptable levels of lead. Use cautiously with achlorhydria (absence of hydrochloric acid in gastric juices) or arrhythmia (irregular heartbeat). Calcium appears to be safe in pregnant or breastfeeding women. Talk to a healthcare provider to determine appropriate dosing during pregnancy and breastfeeding.


Good scientific evidence

  • Magnet therapy
    : Several studies report that pulsed electromagnetic fields may improve the healing of fractures that have not healed properly, including long bone, scaphoid, metatarsal (foot bone), and vertebral fractures. The bone that is the subject of the most research is the tibia (the main long bone in the lower leg). Failure to heal (“non-union”) is usually diagnosed after six to nine months with an X-ray. Pulsed electromagnetic field therapy has been used in Europe and the United States, but remains controversial. It is not clear if this therapy is equal to or better than other therapies, such as bone grafting. This type of treatment requires special equipment and expertise.

  • In theory, pulsed electromagnetic fields may assist with the management of other types of fractures that have failed to heal completely. However, there is not enough evidence to evaluate the use of electrical stimulation for fracture non-unions of other bones in the body other than the long bones. Further research is necessary before a firm conclusion can be drawn. This therapy has not been specifically studied in people with OI.
  • Avoid with implantable medical devices such as heart pacemakers, defibrillators, insulin pumps, or hepatic artery infusion pumps. Avoid with myasthenia gravis or bleeding disorders. Avoid if pregnant or breastfeeding. Magnet therapy is not advised as the sole treatment for potentially serious medical conditions and it should not delay the time to diagnosis or treatment with more proven methods. Patients are advised to discuss magnet therapy with a qualified healthcare provider before starting treatment.
  • Vitamin D
    : Without sufficient vitamin D, inadequate calcium is absorbed and the resulting elevated parathyroid (PTH) secretion causes increased bone resorption. This may weaken bones and increase the risk of fracture. Vitamin D supplementation has been shown to slow bone loss and reduce fracture, particularly when taken with calcium. Avoid if allergic or hypersensitive to vitamin D or any of its components. Vitamin D is generally well-tolerated in recommended doses; higher doses may cause toxic effects. Use cautiously with hyperparathyroidism (overactive thyroid), kidney disease, sarcoidosis, tuberculosis, and histoplasmosis. Vitamin D is safe in pregnant and breastfeeding women when taken in recommended doses.


Unclear or conflicting scientific evidence

  • Black tea
    : Early research suggests that chronic use of black tea may improve bone mineral density (BMD) in older women. Better research is needed in this area before a conclusion can be drawn. Black tea is made from the dried leaves of Camellia sinensis, a perennial evergreen shrub. Black tea has a long history of use, dating back to China approximately 5,000 years ago. Green tea, black tea, and oolong tea are all derived from the same plant. Avoid if allergic or hypersensitive to caffeine or tannins. Use cautiously with diabetes or liver disease. The use of black tea has not been studied specifically in patients with OI.

  • Boron
    : Boron is a trace element that is found throughout the environment. It has been suggested for numerous medicinal purposes, but there is not strong evidence for any specific use. Animal and early human studies report that boron may play a role in mineral metabolism, with effects on calcium, phosphorus, and vitamin D. However, research of bone mineral density in women taking boron supplements does not clearly demonstrate benefits in osteoporosis. Additional study is needed before a firm conclusion can be drawn.

  • Avoid if allergic or sensitive to boron, boric acid, borax, citrate, aspartate, or glycinate. Avoid with a history of diabetes, seizure disorder, kidney disease, liver disease, depression, anxiety, high blood pressure, skin rash, anemia, asthma, or chronic obstructive pulmonary disease (COPD). Avoid with hormone-sensitive conditions like breast cancer or prostate cancer. Avoid if pregnant or breastfeeding.
  • Chromium
    : There is a lack of evidence for or against the use of chromium for the treatment of bone resorption in postmenopausal women. Chromium is an essential trace element that exists naturally in trivalent and hexavalent states. Trivalent chromium (chromium/Cr III), typically found in foods and supplements, appears to have very low toxicity and a wide margin of safety. Hexavalent chromium (chromic oxide, chromate) is a known toxin, and long-term occupational exposure may lead to skin problems, a perforated nasal septum, and lung cancer. Chromium may alter blood sugar levels, which should be closely monitored in people with diabetes. The use of chromium has not been studied specifically in patients with OI.

  • Copper
    : Osteopenia and other abnormalities of bone development related to copper deficiency may occur in copper-deficient low-birth weight infants and young children. Supplementation with copper may be helpful in the treatment and/or prevention of osteoporosis, although early human evidence is conflicting. The effects of copper deficiency or copper supplementation on bone metabolism and age-related osteoporosis require further research before clear conclusions can be drawn.

  • Avoid if allergic/hypersensitive to copper. Avoid the use of copper supplements during the early phase of recovery from diarrhea. Avoid with hypercupremia (an abnormally high concentration of copper in the blood), which occasionally occurs in disease states, including cutaneous leishmaniasis, sickle-cell disease, unipolar depression, breast cancer, epilepsy, measles, Down’s syndrome, or controlled fibrocalculous pancreatic diabetes (a unique form of secondary diabetes mellitus). Avoid with genetic disorders affecting copper metabolism, such as Wilson’s disease, Indian childhood cirrhosis, or idiopathic copper toxicosis. Avoid with HIV/AIDS. Use cautiously with water-containing copper concentrations greater than six milligrams per liter. Use cautiously with anemia, arthralgia (joint pain), or myalgia (muscle pain). Use cautiously if taking oral contraceptives. Use cautiously if at risk for selenium deficiency. The Recommended Dietary Allowance (RDA) is 1,000 micrograms for pregnant women. The RDA for nursing women is 1,300 micrograms.
  • Gamma linolenic acid
    : Gamma linolenic acid (GLA) is a dietary fatty acid. It is found in many plant oil extracts. A limited amount of GLA is found naturally in human breast milk, cold-water fish, and organ meats, such as liver. GLA is commonly sold as a dietary supplement either in the form of capsules or oil. Some evidence from clinical study and observations of clinicians and dieticians has suggested that GLA and eicosapentaenoic acid (EPA) enhance the effects of calcium supplementation in elderly patients with senile osteoporosis. More clinical studies are required to produce results to determine the effectiveness in diverse elderly and middle-aged populations. Use cautiously with drugs that increase the risk of bleeding, such as anticoagulants and anti-platelet drugs. Avoid if pregnant or breastfeeding.

  • Horsetail
    : Silicon may be beneficial for bone strengthening. Because horsetail contains silicon, it has been suggested as a possible natural treatment for osteoporosis. Preliminary human study reports benefits, but more detailed research is needed before a firm recommendation can be made. People with osteoporosis should speak with a qualified healthcare provider about possible treatment with more proven therapies.

  • Hypnosis
    : Results from early research on the effects of hypnosis on bone fractures are inconclusive. Additional study is needed before a firm conclusion can be drawn. This therapy has not been studied specifically in patients with OI. Use cautiously with mental illnesses like psychosis/schizophrenia, manic depression, multiple personality disorder, or dissociative disorders. Use cautiously with seizure disorders. Reported side effects have included changes in skin temperature, heart rate, intestinal secretions and immune response, decreased blood pressure and brain wave patterns, disturbing memories, and false memories.

  • Physical therapy
    : Supervised or home-based physical therapy has been used in combination with resistance and endurance training in physically frail elderly women taking hormone replacement therapy to improve bone density. Although early study is promising, more studies are needed in this area.

  • Not all physical therapy programs are suited for everyone, and patients should discuss their medical history with a qualified healthcare professional before beginning any treatments. Based on the available literature, physical therapy appears generally safe when practiced by a qualified physical therapist. However, complications are possible. Treatment options should be considered carefully. Physical therapy may aggravate pre-existing conditions. Persistent pain and fractures of unknown origin have been reported. Physical therapy may increase the duration of pain or cause limitation of motion. Pain and anxiety may occur during the rehabilitation of patients with burns. Both morning stiffness and bone erosion have been reported in the literature, although causality is unclear. Erectile dysfunction has also been reported. Physical therapy has been used in pregnancy, specifically to treat women with pelvic girdle pain during pregnancy and at three, six, and 12 months postpartum. Reports of major adverse effects are lacking in the available literature, but caution is advised nonetheless. All therapies during pregnancy and breastfeeding should be discussed with a licensed obstetrician/gynecologist before initiation.
  • Red clover
    : Red clover is a legume that contains “phytoestrogens” or plant-based chemicals that are similar to estrogen; it may act in the body like estrogen or may actually block the effects of estrogen. Red clover has been traditionally used to treat asthma, pertussis, cancer, and gout. In modern times, isoflavone extracts of red clover are most often used to treat menopausal symptoms, as an alternative hormone replacement therapy, for high cholesterol, or to prevent osteoporosis. However, at this time, high-quality human studies supporting the use of red clover for any medical condition are lacking. It is not clear if red clover isoflavones have beneficial effects on bone density. Most studies of isoflavones have looked at soy, which contains different amounts of isoflavones, as well as other non-isoflavone ingredients. More research is needed before a recommendation can be made.

  • Soy
    : In theory, “phytoestrogens” in soy (plant-based compounds with weak estrogen-like properties) such as isoflavones may increase bone mineral density in post-menopausal women and reduce the risk of fractures. However, most studies have not been well-designed or reported. Until better research is available, a firm conclusion cannot be drawn. Individuals at risk for osteoporosis should speak with a qualified healthcare provider about the therapeutic options for increasing bone mineral density.

  • Avoid if allergic to soy. Breathing problems and rash may occur in sensitive people. Soy, as a part of the regular diet, is traditionally considered to be safe during pregnancy and breastfeeding, but there is limited scientific data. The effects of high doses of soy or soy isoflavones in humans are not clear and therefore are not recommended. There has been a case report of vitamin D deficiency rickets in an infant nursed with soybean milk (not specifically designed for infants). People who experience intestinal irritation (colitis) from cow’s milk may experience intestinal damage or diarrhea from soy. It is not known if soy or soy isoflavones share the same side effects as estrogens, like increased risk of blood clots. The use of soy is often discouraged in patients with hormone-sensitive cancers, such as breast, ovarian, or uterine cancer. Other hormone-sensitive conditions such as endometriosis may also be worsened. Patients taking blood-thinning drugs like warfarin should check with a doctor and pharmacist before taking soy supplementation.
  • Tai chi
    : Early research suggests that tai chi may be beneficial in delaying early bone loss in postmenopausal women. Additional evidence and long-term follow-up is needed to confirm these results. Avoid with severe osteoporosis or joint problems, acute back pain, sprains, or fractures. Avoid during active infections, right after a meal, or when very tired. Some believe that visualization of energy flow below the waist during menstruation may increase menstrual bleeding. Straining downwards or holding low postures should be avoided during pregnancy and by people with inguinal hernias. Some tai chi practitioners believe that practicing for too long or using too much intention may direct the flow of chi (qi) inappropriately, possibly resulting in physical or emotional illness. Tai chi should not be used as a substitute for more proven therapies for potentially serious conditions. Advancing too quickly while studying tai chi may increase the risk of injury.

  • Vitamin D
    : While Vitamin D supplementation has been shown to slow bone loss and reduce fracture, particularly when taken with calcium, it has not been proven to be an effective therapy for osteogenesis imperfecta (OI) specifically. Additional research is needed in this area.
    Avoid if allergic or hypersensitive to vitamin D or any of its components. Vitamin D is generally well-tolerated in recommended doses; higher doses may cause toxic effects. Use cautiously with hyperparathyroidism (overactive thyroid), kidney disease, sarcoidosis, tuberculosis, and histoplasmosis. Vitamin D is safe in pregnant and breastfeeding women when taken in recommended doses.

  • Vitamin K
    : Vitamin K appears to prevent bone resorption and adequate dietary intake is likely necessary to prevent excess bone loss. Elderly or institutionalized patients may be at particular risk and adequate intake of vitamin K-rich foods should be maintained. Unless patients have demonstrated vitamin K deficiency, there is no evidence that additional vitamin K supplementation is helpful. Some studies show that vitamin K supplements may increase bone mineral density and bone strength, while others show that vitamin K has no effect on bone turnover. However, vitamin K may play a role in the prevention and treatment of glucocorticoid-induced bone loss. Furthermore, vitamin D and calcium supplementation may enhance the beneficial effects of vitamin K. Further research is needed to confirm these results.

  • Avoid if allergic or hypersensitive to vitamin K. Injection into the muscle or vein should only be done by a healthcare professional; many serious side effects have occurred after injection. Menadiol (type of vitamin K that is not available in the United States) should be avoided with glucose-6-phosphate dehydrogenase deficiency. Conditions that interfere with the absorption of ingested vitamin K may lead to deficiency, including short gut, cystic fibrosis, malabsorption (various causes), pancreas or gall bladder disease, persistent diarrhea, sprue, or ulcerative colitis. Avoid if pregnant. Use cautiously if breastfeeding.


Fair negative scientific evidence

  • Thiamin
    : Early evidence shows that supplemental thiamin is not beneficial for hip fractures. Additional research is needed to confirm these results. Thiamin is generally considered safe and relatively nontoxic. Avoid if allergic or hypersensitive to thiamin. Rare hypersensitivity/allergic reactions have occurred with thiamin supplementation. Skin irritation, burning, or itching may rarely occur at injection sites. Large doses may cause drowsiness or muscle relaxation. Thiamin appears safe if pregnant or breastfeeding. Use cautiously if pregnant or breastfeeding.


  • Genetic counseling is recommended for couples considering pregnancy if there is a personal or family history of this condition. Genetic counselors can help people with OI and their family members further understand OI genetics and assist in prenatal diagnosis.

Author Information

  • This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (


Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to Selected references are listed below.

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