Editor's note
The 10th Conference on New Advances in Osteoporosis and Diabetes in the Elderly was successfully held on March 30~31, 2024. This conference invited well-known domestic experts to discuss the new concepts, new achievements and new difficulties in the treatment of osteoporosis and diabetes in the elderly. In response to the topic of "Diagnosis and Differential Diagnosis of Osteoporosis (OP)", Professor Wang Aihong from the Department of Endocrinology of the Characteristic Medical Center of the Strategic Support Force made a wonderful academic sharing. Now sort out its essence and enjoy it with you.
1. Definition and epidemiology of OP
According to the World Health Organization (WHO) definition [1]: OP is a systemic bone disease characterized by low bone mass, damage to bone microstructures, increased bone fragility, and susceptibility to fractures. The National Institutes of Health (NIH) defines [2]: OP is a disease of the skeletal system characterized by decreased bone strength and an increased risk of fractures. The continent currently uses the WHO definition.
Osteoporotic fractures: also known as fragility fractures, are fractures that occur after minor trauma (equivalent to a fall from standing height or lower) and are a serious consequence of OP [3].
According to a 2018 epidemiological survey of OP involving more than 20,000 people [4], it is estimated that the number of OP patients in mainland China is about 90 million, of which about 70 million are women.
Figure 1. The prevalence of OP in mainland China (chart from: a picture to understand the results of the epidemiological survey of osteoporosis in China.Healthy China Health News, 2022-09-10.)
2. Diagnosis of OP
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Clinical presentation
Pain: Caused by decreased skeletal mechanical properties and microfractures, mainly manifested as low back pain or generalized bone pain, aggravated at night or during weight-bearing activities, and may be accompanied by muscle spasms and limited mobility.
Spinal deformation: caused by vertebral compression fracture, short height, spinal hunchback deformity, severe cases due to spinal cord nerve compression or abnormal cardiopulmonary function and abdominal organ function, constipation, abdominal pain, bloating, loss of appetite and other discomforts.
Fracture: It is a fragility fracture, which can be the first symptom, and the common sites are the vertebral body (thoracic and lumbar vertebrae), hip (proximal femur), distal forearm and proximal humerus, among which vertebral fracture is the most common. After an osteoporotic fracture occurs, the risk of refracture increases significantly.
02
INVESTIGATIONS[3]
(1) Imaging examination
Dual-energy X-ray absorptiometry (DXA): the most commonly used method of bone densitometry, it is now recognized as the "gold standard" for the diagnosis of OP. It can be used for OP diagnosis, fracture risk prediction, drug efficacy evaluation and epidemiological research. The main measurement site is the axial bone (lumbar spine and proximal femur), and in one of the following situations: bone mineral density cannot be measured at the lumbar spine or proximal femur, and patients with hyperparathyroidism and receiving androgen deprivation therapy for prostate cancer can take the distal 1/3 of the radius on the non-dominant side as the measurement site.
X-ray: the preferred method to check for thoracic and lumbar compression fractures. Lateral x-rays of the thoracic and lumbar spine are recommended in the following conditions (table 1) to check for vertebral fractures. Vertebral compression fractures can be classified into I., II., III., or mild, moderate, or severe according to the degree of compression (Fig. 2).
Figure 2. Genant is a method of visual semi-quantitative determination of vertebral fractures
Other imaging tests
(1) CT is more sensitive to show subtle fractures, and MRI can show early bone marrow changes and bone marrow edema, both of which can be used for differential diagnosis with a variety of other bone diseases.
(2) Nuclear medicine examination: used to distinguish secondary OP and other bone diseases.
(3) Quantitative computed tomography (QCT): it can measure the volume density of cancellous bone and cortical bone respectively, and can sensitively reflect the loss of cancellous bone in the early stage of OP. It is more accurate to measure bone mineral density in patients with obesity, spinal degeneration, or abdominal aortic calcification, but no unified QCT diagnostic criteria have been established internationally.
(4) Peripheral quantitative CT (pQCT), peripheral dual-energy X-ray absorptiometry (pDXA), single-energy X-ray bone mineral density (SXA), radioresorptometry (RA), quantitative ultrasound (QUS): used for peripheral bone density measurement, only for screening people at risk of osteoporosis.
(6) Trabecular bone score (TBS): It is a new index derived from DXA, which is a gray-scale structure index based on DXA images, as a useful supplement to bone mineral density, providing information other than bone density.
(2) Laboratory tests
General examination items (to assist in differential diagnosis): blood routine, urine routine, erythrocyte sedimentation rate, liver and kidney function, serum calcium, blood phosphorus, blood alkaline phosphatase, 25-hydroxyvitamin D, parathyroid hormone levels, and urine calcium, urine phosphorus, and urine creatinine.
Biochemical markers of bone turnover (BTMs): intermediate metabolites or enzymes produced during bone transition, which are divided into bone formation markers and bone resorption markers, the former reflecting osteoblast activity and bone formation status, and the latter reflecting osteoclast activity and bone resorption level. BTMs cannot be used in the diagnosis of OP, but they can assist in differential diagnosis, determine the type of bone turnover, predict fracture risk, monitor treatment adherence, and evaluate drug efficacy.
Table 2. Classification of BTMs
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Diagnostic criteria[3]
(1) Diagnosis based on DXA bone mineral density
For postmenopausal women, men aged 50 years and older: Bone density levels are expressed using T-scores. T-value = (measured value of bone mineral density - peak bone mineral density of normal young people of the same race and sex) / standard deviation of peak bone mineral density of normal young people of the same race and sex
Normal: T-score ≥-1, osteopenia: -2.5< T-score <-1, osteoporosis: T-score ≤-2.5.
For children, premenopausal women, and men under 50 years of age: Bone mineral density levels are expressed using Z-scores. Z-value = (bone densitometry value - mean bone mineral density of people of the same race and sex and the same age)/standard deviation of bone mineral density of people of the same race and sex and the same age
Low bone mass or "below the expected range for the age group": Z-score ≤-2.0.
(2) Diagnosis based on fragility fractures
Fragility fractures of the hip or vertebrae are clinically diagnosed without relying on bone densitometry, and fragility fractures of the proximal humerus, pelvis, or distal forearm are diagnosed by low bone mass (-2.5<T-value <-1.0) on bone densitometry.
Table 3. Diagnostic criteria for OP
04
Risk assessment of OP[3]
Assessment tools include the International Osteoporosis Foundation (IOF) Osteoporosis Risk One-Minute Test Questions, the Asian Osteoporosis Self-Screening Tool (OSTA), and the Risk Prediction for Osteoporotic Fractures (FRAX). The results suggest that the current FRAX prediction results may underestimate the fracture risk in the mainland population, and there are regional and ethnic differences, which still need to be improved.
Table 4. OSTA index grading
3. Classification of OP
Depending on the etiology, OP is divided into two categories: primary and secondary.
Secondary OP: refers to osteoporosis caused by any disease and/or drug or other established cause that affects bone metabolism. Certain diseases such as diabetes, hyperthyroidism, hematologic diseases, other metabolic bone diseases, tumors, kidney diseases, etc., drugs such as anti-epileptic drugs, glucocorticoids or other immunosuppressants, etc., and other factors.
Primary OP: Osteoporosis with the exception of the above secondary causes, including postmenopausal osteoporosis (type I), senile osteoporosis (type II), and idiopathic osteoporosis (juvenile type). BTMs levels are usually normal or mildly elevated in patients with primary OP. If BTMs levels are markedly elevated, high-conversion secondary OP or other metabolic bone disorders should be excluded.
Figure 3. Primary OP typing
4. Differential diagnosis of OP
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Differentiation of etiology
The main causes that need to be identified include: endocrine diseases that affect bone metabolism, autoimmune diseases such as rheumatoid arthritis, digestive tract and kidney diseases that affect the absorption and metabolism of calcium and vitamin D, neuromuscular diseases, malignant diseases such as multiple myeloma, a variety of congenital and acquired abnormal bone metabolism diseases, and long-term use of glucocorticoids or other drugs that affect bone metabolism.
Other metabolic bone diseases: such as osteomalacia, osteogenesis imperfecta.
Secondary OP in endocrine diseases: hyperparathyroidism, Cushing's syndrome, hyperthyroidism, hypogonadism, anterior hypopituitarism.
02
Diabetes-related OP
Numerous studies have confirmed diabetes as an independent risk factor for fragility fractures. Meta-analysis suggests that the risk of hip fracture in patients with type 1 diabetes is 4~6 times higher than that of non-diabetic patients [5], and the risk of hip fracture in patients with type 2 diabetes is 1.3 times higher than that of non-diabetic patients [6].
(1) Mechanism of OP caused by diabetes
Complications: Weakening bone strength (diabetic neuropathy), increasing the probability of falls (diabetic retinopathy, diabetic neuropathy), weakening bone nutrient supply (diabetic microangiopathy), etc., increasing the occurrence of osteoporotic fractures.
Sugar control: On the one hand, the risk of osteoporosis is reduced by reducing the impact of glycation end products on bone metabolism and delaying the occurrence and development of complications, and on the other hand, the probability of hypoglycemic events is increased and the risk of fragility fractures is increased.
(2) Risk factors for fractures specific to diabetes
lumbar or hip T-score ≤2; frequent hypoglycemic events; duration of diabetes > 10 years; diabetes medications such as insulin, thiazolidinedione, sulfonylurea; HbA1c >8%; peripheral and autonomic neuropathy; retinopathy and nephropathy.
(3) Diagnosis and treatment recommendations for diabetes-related OP
Figure 4. Recommendations for diabetic osteoporosis[7]
5. Summary
OP can be caused by a variety of etiologies, and before diagnosing OP, it is important to pay attention to and exclude other factors affecting bone metabolism to avoid missed diagnosis or misdiagnosis. A detailed history is required to evaluate the various causes, risk factors, and medications that may contribute to OP. According to the clinical symptoms and signs of the patient, the correct diagnosis and differential diagnosis of patients with diagnosed and clinically suspected osteoporosis are carried out with the help of auxiliary examinations (including laboratory tests and skeletal X-rays).
Figure 5. Osteoporosis Diagnosis and Treatment Procedure[3]
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3. Guidelines for the diagnosis and treatment of primary osteoporosis (2022).Chinese Journal of General Practice, 2023,26 (14): 1671-1691.
4. Epidemiological survey report of osteoporosis in China (2018) [M]. Beijing: People's Medical Publishing House, 2021.
5. Shah VN, Shah CS, Snell-BergeonJK (2015) Type 1 diabetes and risk of fracture: meta-analysis and review of the literature. DiabetMed 32:1134–1142.
6. Fan Y, Wei F, Lang Y, Liu Y (2016) Diabetes mellitus and risk of hip fractures: a meta-analysis. OsteoporosInt 27:219–228.
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