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Kendall Moseley, M.D, and Todd T. Brown, M.D, Ph.D.
02-04-2011
- Osteoporosis and osteopenia are the most important bone diseases observed in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), characterized by decreased bone mass and structural deterioration of bone tissue, leading to bone fragility and increased susceptibility to fracture.
- On bone density measurements via dual energy X-ray absorptiometry (DXA): a T-score between 1.0 and -1.0 standard deviations (SD) is considered normal bone density, a score between -1.0 to -2.5 SD is osteopenia and a score that is below -2.5 SD is osteoporosis; Z-scores used for men < 50 years and premenopausal women.
- Osteomalacia is softening of the bone resulting from impaired bone mineralization with calcium and vitamin D.
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Charcot foot is a result of bone loss in the foot or ankle causing microfractures, ligament laxity and bony destruction, then exacerbated by neuropathy and patient's inability to perceive ongoing trauma.
- According to the National Osteoporosis Foundation (NOF), low bone mass affects over 55% of persons greater than 50 years of age; in the U.S., greater than 10 million people have osteoporosis, while 34 million have low bone mass.
- Prevalence of osteoporosis and osteopenia varies in T1DM depending on whether individual has reached peak bone mass, duration of diabetes, and degree of glycemic control (Mastrandrea).
- Among middle-aged persons with T1DM, 30-60% have osteopenia and 10-30% have osteoporosis when compared to age-matched controls (Wada).
- Bone density, on average, higher in T2DM when compared to healthy control subjects, although this population may be more susceptible to fracture at the hip and non-vertebral sites, described below (Vestergaard).
- Prevalence and incidence of low bone mass and fracture in T2DM varies and depends upon disease control, duration, and degree of end-organ damage (i.e., neuropathy, nephropathy, retinopathy, etc.) (Leidig-Bruckner).
- See definition section for specific diagnostic criteria.
- Dual energy X-ray absorptiometry (DXA) is the gold standard for areal densiometry measurements
- Quantitative CT scan and calcaneal ultrasound are alternative modalities for bone mineral density (BMD) measurement.
- Screening: No specific guidelines for osteoporosis or osteopenia in diabetes mellitus
- Current NOF general recommendations: bone density testing in women >65 years or men >70 years if no risk factors for osteoporosis (Heinemann)
- Screening for men and women >50 years if one or more risk factors for osteoporosis or bone disease (i.e., steroid use, hyperparathyroidism, malnutrition, maternal hip fracture)
- Screening for men and women, regardless of age, if there is a history of fragility fracture
- Incidental identification of low bone mass or poor bone mineralization may be diagnosed on routine X-rays
- Low serum 25-hydroxyvitamin D level (<15 ng/mL) with concurrent elevated intact parathyroid hormone (iPTH) may herald osteomalacia
- Elevated serum iPTH level observed in secondary hyperparathyroidism due to renal disease or vitamin D deficiency can lead to bone disease
- Signs and symptoms of bone disease the same for persons with and without diabetes mellitus
- Osteoporosis and osteopenia usually clinically silent diseases
- Low-trauma fractures or recurrent fractures at any age in T1DM or T2DM should raise suspicion of bone disease
- Fragility fractures resulting from low bone density a major source of osteoporosis-induced pain and morbidity
- Sudden onset in focal back pain or spinal process tenderness to physical exam could indicate vertebral fracture
- Severe hip pain, hip swelling, and inability to walk following a fall could indicate hip fracture
- Severe vitamin D deficiency may manifest as bone pain and fatigue
- Increased prevalence of celiac disease and vitamin D deficiency in T1DM; symptoms including abdominal pain, bloating, and diarrhea
- Bowing of the legs in childhood observed with vitamin D deficiency/rickets in children
- Optimize glycemic control to minimize advanced glycation end-product (AGE) deposition in bone (Schwartz)
- Optimize glycemic control to minimize malnutrition, especially in early T1DM
- HbA1C < 7% to minimize microvascular and macrovascular complications which can contribute to and exacerbate bone disease and fall risk (Schwartz)
- Retinopathy and neuropathy screening, prevention, and treatment for fall and fracture reduction
- Nephropathy prevention and treatment to normalize calcium, phosphate, and vitamin D handling
- Prevention and reduction of peripheral and microvascular disease to optimize blood supply to bone and maintain bone quality
- Orthostatic hypotension, if untreated, may increase fall and fracture risk in persons with autonomic dysfunction
- Minimize hypoglycemic episodes which can lead to syncope, falls, and fractures (Schwartz)
- NOF dietary and lifestyle recommendations apply to general and diabetic population with bone disease.
- Calcium 1,000 mg and vitamin D 400-800 IU daily in adults < 50 years-old; calcium 1,200 mg and vitamin D 800-1000 IU daily in adults > 50 years-old and in those with known bone disease
- Consider dietary supplements if inadequate intake in food sources alone or if malabsorption present
- High-dose vitamin D repletion for vitamin D deficiency or insufficiency with ergocalciferol or cholecalciferol
- Protein intake up to 15% of daily caloric intake
- Maintain healthy weight (BMI 18.5-24.9 kg/m2)
- Weight bearing exercise and resistance exercises to strengthen bone (i.e. biomechanical forces) (Daly)
- Moderate aerobic exercise for cardiovascular health and weight maintenance
- Home safety evaluation and hazard identification for fall prevention
- Hip protectors of potential benefit in the elderly
- If osteoporosis present and/or high risk for fracture, pharmacotherapy often needed in addition to exercise, calcium, and vitamin D (see expert comments on FRAX calculations); therapeutic options the same for persons with and without diabetes mellitus.
- Anti-resorptive medications to inhibit osteoclast-mediated bone resorption but use limited to those without renal failure
- Bisphosphonates most common anti-resorptive medications (alendronate, risedronate, ibandronate, zoledronic acid)
- Dose recommendations: alendronate 70mg orally weekly; risedronate 35mg orally weekly OR 150mg monthly; ibandronate 150mg orally monthly; zoledronic acid 5mg IV yearly
- Raloxifene, an anti-resorptive and a selective estrogen receptor modifier (SERM): dose 60mg orally daily
- Denosumab, a monoclonal antibody against RANK ligand, awaiting approval as newest anti-resorptive medication on the market
- Teriparitide (recombinant PTH) the only approved anabolic therapy on the market for treatment of osteoporosis; dose 20mcg SQ daily for up to 2 years
- Estrogen and/or hormone replacement therapy, controversial in post-menopausal osteoporosis treatment (cardiovascular complications)
- Testosterone in hypogonadal men beneficial to bone
- When possible, avoid medications which might have adverse effects on bone metabolism (steroids, anti-epileptic medications, thiazolidinediones in those with known bone disease) (Kahn)
- Physical therapy to optimize core strength and transfers, minimize falls and fracture risk.
- Vertebroplasty and fixation for vertebral pain management and spine stabilization.
- Orthopedic specialist required for Charcot foot management including limited weight bearing, total contact casting, possible surgical intervention.
- Diagnose and treat other secondary causes of bone loss (i.e., Cushing's disease, primary hyperparathyroidism, rheumatoid arthritis).
- Typical work-up of secondary causes of osteoporosis: iPTH, 24-hour urine calcium, testosterone, SPEP, UPEP, phosphate, magnesium, 25-hydroxyvitamin D (consider 1,25 hydroxyvitamin D in patients with renal disease).
- Fractures, bone pain
- Fall history, syncope
- Kidney stones (hypercalciuria)
- New medications which might worsen bone loss (i.e., thiazolidinediones, steroids, anti-seizure, breast or prostate cancer therapies, etc.)
- Compliance or side effects with osteoporosis medications
- Height loss, worsening kyphosis
- Point tenderness to spinal process palpation, anterior tibial pain
- Diabetes management per routine
- No definite screening guidelines for vitamin D deficiency, but consider yearly serum levels of 25-hydroxyvitamin D
- If progressive bone loss despite therapy, re-address other secondary causes of osteoporosis
- Consider measurement of markers of bone resorption (N-telopeptide or C-telopeptide) if person on long-standing pharmacotherapy with question of efficacy
- Measure serum uric acid and calcium two weeks after teriparitide initiation
- Vertebral fracture evaluation with PA/lateral spine X-rays for new back pain, point tenderness
- DXA yearly to every two years in those initiated on osteoporosis therapy
- DXA yearly in those with low bone density being monitored for therapy initiation
- Repeat DXA in those with previously normal bone density who have suffered a new fracture
- Although T2DM associated with higher BMD on DXA than healthy age-matched population, fracture risk may be up to two-fold higher (Vestergaard)
- Mainstay of improving insulin sensitivity in T2DM is weight loss, although BMD may also decrease with body mass index
- PPAR gamma agonists (thiazolidnediones) influence mesenchymal stem cell differentiation into adipocytes rather than osteoblasts, leading to bone loss and increased risk of fracture; prescription of TZDs should be limited to those considered at low risk for bone disease (Vestergaard)
- Fracture risk assessment tool, FRAX (http://www.shef.ac.uk/FRAX/index.htm), aids in calculating 10-year major osteoporotic and hip fracture risk based on patient information and risk factors for bone loss; type 1 diabetes considered secondary cause of osteoporosis in this model
- Consider and screen for syndromes with combined osteoporosis and diabetes phenotype in the appropriate patient: Klinefelter's syndrome, Turner's syndrome, Cushing's syndrome, polyglandular autoimmune syndrome type II, and hereditary hemochromatosis
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