Osteogenesis imperfecta

Disease Description (Causes and Symptoms)

• Definition: A disease in which bone strength becomes weakened and the risk of fractures increases due to a decrease in bone mass and microstructure. Most adult bone mass is formed during puberty, bone mass gradually decreases after age 35, and rapid bone-density loss is common during the 3–5 years after menopause.
• Pathophysiology: An imbalance between bone resorption (osteoclasts) and bone formation (osteoblasts) causes bone resorption to predominate. In particular, estrogen deficiency promotes osteoclast activity through increased RANKL.
• Major causes (primary/secondary): Older age and menopause (primary); chronic steroid use, Cushing syndrome, hyperparathyroidism, malabsorption (intestinal surgery and inflammatory bowel disease), chronic kidney or liver disease, anticonvulsants, heparin, excessive thyroid hormone, etc. (secondary). Family history, lack of exercise, low calcium or vitamin D, excessive alcohol consumption, smoking, and other factors also contribute.
• Major symptoms: Initially asymptomatic. As the disease progresses, low back pain, loss of height, and kyphosis (rounded back) due to vertebral compression fractures may occur, along with an increased incidence of fractures of the wrist, hip, and spine caused by minor trauma or daily activities.

Treatment Methods

• Diagnostic criteria and evaluation: Blood tests to investigate secondary causes (calcium, phosphorus, albumin, creatinine, vitamin D, PTH, TSH, etc.), and bone-density testing (DEXA) using T-score criteria: normal ≥ −1.0, osteopenia −1.0 to −2.5, osteoporosis ≤ −2.5. Use of fracture-risk calculators such as FRAX is recommended.
• Drug treatment (major current standards)
  • First-line: Bisphosphonates (oral: alendronate, risedronate / IV: zoledronic acid) — inhibit bone resorption and reduce fracture risk.
  • Biologic agent: denosumab (anti-RANKL) — injectable, with a strong bone-density-increasing effect (caution regarding rebound effects after discontinuation).
  • Bone formation stimulators: teriparatide (a parathyroid hormone analog), abaloparatide — may be considered for severe osteoporosis.
  • Selective estrogen receptor modulator (SERM: raloxifene) — maintains bone density and reduces vertebral fractures (may reduce breast cancer risk).
  • Hormone therapy (estrogen): May be considered when menopausal symptoms and bone loss occur simultaneously, but long-term adverse effects (breast cancer, blood clots, etc.) must be considered.
  • Supplements: Calcium (general recommended amount for adults: 1,000–1,200 mg/day, from diet plus supplements), vitamin D (optimize blood 25(OH)D levels with a target of 800–2,000 IU/day).
  • Other (limited use): Calcitonin (pain relief), strontium preparations (used in some countries), sodium fluoride (limited current use).
• Procedures/surgery: Orthopedic surgery is required for hip fractures and complex fractures. Vertebroplasty/kyphoplasty may be considered for severe vertebral compression fractures (indications are limited).
• Lifestyle management and prevention: Weight-bearing and strength exercises (walking, running, jumping and high-jump exercises, etc., according to age and condition), fall prevention (improving the home environment, vision care, and walking aids), smoking cessation and moderation of alcohol, a low-salt diet (excessive sodium increases calcium excretion), limiting excessive caffeine, and adequate protein intake. Regular exposure to sunlight (for example, about 15 minutes twice a week) may help with vitamin D synthesis.
• Precautions during treatment
  • Take oral bisphosphonates on an empty stomach with water and do not lie down for 30–60 minutes afterward (they can interfere with food and other medications). They may be contraindicated in patients with esophageal disease.
  • Although rare, be aware of the risks of osteonecrosis of the jaw and atypical femoral fractures when using bisphosphonates or denosumab; evaluation and prevention are needed before dental procedures.
  • Discontinuation of denosumab carries a risk of rapid bone-density loss and increased vertebral fractures, so alternative treatment (e.g., bisphosphonates) should be considered when planning discontinuation.
• Monitoring: DEXA testing at 1–2-year intervals after starting treatment (depending on individual risk and treatment response), as well as blood calcium, vitamin D, kidney-function tests, and other tests as needed.

Outpatient Visit Checklist (Preparation Items, Information to Record, and Sample Questions)

• Items to prepare/bring
  • A list of all medications and supplements currently being taken (including doses and duration of use)
  • Previous test results and DEXA results, if available
  • A record of fracture history (circumstances at the time of injury) and falls
  • Menstrual history and timing of menopause (women), and family history (whether parents or siblings have had fractures)
  • Lifestyle records (alcohol consumption, smoking, amount of exercise, eating patterns)
  • Recent weight changes and changes in physical function (walking pattern, balance, etc.)
• Examples of symptoms to record and tell the doctor in advance during the visit
  • Recent back pain, loss of height, or changes in back shape (kyphosis)
  • Whether pain or fractures have occurred due to minor trauma
  • Newly started medications (such as steroids) or medications that have been discontinued
• Tests and evaluations expected at the outpatient visit
  • Blood tests (calcium, phosphorus, creatine, 25(OH)D, PTH, TSH, etc.), DEXA (bone density), and, if necessary, spinal X-rays to check for compression fractures.

Examples of General Questions to Ask the Doctor

• "What are my bone density (T-score) and fracture risk (FRAX) values? Do I need treatment?"
• "What are the major side effects and precautions of the prescribed medication?"
• "How long should I take this medication? What problems can occur if I stop it?"
• "Which activities or foods should I particularly avoid, and what specific exercises are recommended?"
• "I need dental treatment (such as a tooth extraction). What should I prepare in relation to taking this medication?"

Examples of Disease-Specific Questions

• Patients suspected of having postmenopausal osteoporosis: "Considering the timing and symptoms of menopause and the benefits and risks of hormone replacement therapy, is hormone therapy appropriate for me?"
• Patients taking long-term steroids: "What medication, such as a bisphosphonate, should I start immediately to prevent osteoporosis caused by long-term steroid use, and what is the monitoring plan?"