Quiz of the week

23 years old male patent who presented with sudden onset of sever back pain and his MRI of spine shows a fracture. How do you approach this case based on history and investigation?

osteoprosis Dr.zainab al-shehab

difinition Osteoporosis is a skeletal condition characterized by low bone mass, which is associated with reduced bone strength and an increased risk of fractures.

Low bone mass The measurement of bone mineral density (BMD) by dual- energy x-ray absorptiometry (DXA) is used as an index of bone strength and fracture risk, and can be used to diagnose osteoporosis in some populations, such as postmenopausal women. The World Health Organization (WHO) defines osteoporosis in postmenopausal women as: a BMD value at the spine, hip, or forearm of 2.5 or more SD (standard deviations) below the young adult mean (T-score ≤- 2.5), with or without the presence of a fragility fracture

premenopausal women the prevalence of fractures is much lower compared with postmenopausal women, and the relationship between BMD and fracture risk is not the same. Thus, neither the diagnostic guidelines nor the treatment practices based on bone density measurements. The International Society for Clinical Densitometry (ISCD) recommends use of BMD Z-scores (comparison to age- matched norms) at the lumbar spine, total hip, femoral neck, and distal radius, rather than T-scores, and avoidance of the term osteopenia A Z-score ≤-2.0 should be interpreted as “below the expected range for age” BMD measurements alone should not be used to define osteoporosis in premenopausal women.

Definition in premenepausal According to the ISCD, a young woman with low BMD for age (Z-score ≤-2.0) and with risk factors for fracture or secondary causes of osteoporosis (such as glucocorticoid therapy, hypogonadism, or hyperparathyroidism) may be defined as having premenopausal osteoporosis

Low-trauma fracture Any fracture in an adult woman (aside from a fracture of the digits) that occurs from a standing height or less, without major trauma such as a motor vehicle accident, can be considered a low-trauma or fragility fracture. Such women may have decreased bone strength and may be considered to have osteoporosis, irrespective of BMD

prevelence Vertebral fractures can occur despite normal BMD in women receiving glucocorticoids. One study found that 7 of 16 premenopausal women treated with high-dose glucocorticoids had evidence of vertebral fractures despite normal BMD

Secondary causes of osteoporosis in premenopausal women

Anorexia nervosa Gastrointestinal malabsorption (eg, celiac disease, postoperative states) Vitamin D and/or calcium deficiency Hyperthyroidism Hyperparathyroidism Cushing's syndrome Hypogonadism (hypogonadotropic or hypergonadotropic) Diabetes (types 1 and 2) Hypercalciuria Rheumatoid arthritis and other inflammatory conditions Alcoholism

Marfan's syndrome and Ehlers-Danlos syndrome Homocystinuria Hereditary homochromatosis Thalassemia major Gaucher disease HIV infection and/or medications Renal disease Liver disease Osteogenesis imperfecta Systemic mastocytosis

Medications Glucocorticoids Immunosuppressants (cyclosporine) Antiseizure medications (particularly phenobarbital and phenytoin) GnRH agonists (when used to suppress ovulation) Heparin Chemotherapy leading to amenorrhea Thiazolidinediones Depot medroxyprogesterone acetate Possible contributors Excess thyroid hormone Depression and/or SSRI use Proton pump inhibitors

How to approach?

all premenopausal women with low BMD and/or fragility fracture have the following basic tests ●Complete blood count ●Calcium, phosphate, creatinine ●Alkaline phosphatase, aminotransferases ●25-hydroxyvitamin D ●Thyroid-stimulating hormone (TSH)

Additional laboratory tests if indicated 24 hour urine for free cortisol Estradiol, LH, FSH, prolactin Magnesium 1,25 dihydroxyvitamin D Intact PTH Celiac screen Serum protein electrophoresis/urine protein electrophoresis Erythrocyte sedimentation rate Rheumatoid factor Ferritin and carotene levels Iron and total iron binding capacity Serum tryptase and histamine levels Homocysteine COL1A genetic testing for osteogenesis imperfecta Serum and urine markers of bone turnover

BMD Results are generally scored by two measures, the T-score and the Z-scoreT-scoreZ-score Negative scores indicate lower bone density, and positive scores indicate higher

T-score It is the bone mineral density (BMD) at the site when compared to the young normal reference mean. It is a comparison of a patient's BMD to that of a healthy thirty-year- old. Normal is a T-score of -1.0 or higher Osteopenia is defined as between -1.0 and -2.5 Osteopenia Osteoporosis is defined as -2.5 or lower, meaning a bone density that is two and a half standard deviations below the mean of a thirty-year-old man/woman Osteoporosis

Z-score The Z-score is the comparison to the age-matched normal and is usually used in cases of severe osteoporosis. This is the number of standard deviations a patient's BMD differs from the average BMD of their age, sex, and ethnicity. This value is used in premenopausal women, men under the age of 50, and in children It is most useful when the score is less than 2 standard deviations below this normal.

Serial BMD measurements Some women may have genetically determined low peak bone mass. Other women may have accrued less bone than expected due to insults to the skeleton (eg, medications, poor nutrition, estrogen deficiency) that occurred during adolescence and are no longer present at the time of evaluation. In either case, these women should have stable BMD, even though BMD is low. This is in contrast to women with continued declines in BMD who may have an ongoing secondary cause. Serial BMD measurements, if available, are helpful in making this distinction

Biopsy?! In patients with a history of fragility fractures without a known cause, iliac crest bone biopsy may be indicated to identify other sources of bone fragility and to guide therapeutic interventions

management

premenepausal Calcium vitamin D, weight bearing exercise Pharmacologic therapies that have shown antifracture efficacy in postmenopausal women However, there are very few data available to guide clinicians in the use of these medications in premenopausal women and virtually no data on efficacy or safety of these therapies in premenopausal women without secondary causes of osteoporosis. As a result, treatment with medications is usually reserved for those with : 1-fracture(s), 2-active bone loss, and/or known ongoing secondary causes of osteoporosis and bone loss.

postmenepausal

Patients with the highest risk of fracture are the ones most likely to benefit from drug therapy. Fracture risk is determined by a combination of bone mineral density (BMD) and clinical risk We calculate fracture risk using the World Health Organization (WHO) Fracture Risk Assessment Tool (FRAX)

postmenepausal

bisphosphonates For most postmenopausal women with osteoporosis, we suggest oral bisphosphonates as first-line therapy. We prefer oral bisphosphonates as initial therapy because of their efficacy, favorable cost, and the availability of long-term safety data. Alendronate 70mg po once weekly Alendronate risedronate

zoledronic acid Intravenous (IV) zoledronic acid, which has been demonstrated to reduce vertebral and hip fractures, is available in many countries for the treatment of postmenopausal osteoporosis. It is a good alternative for individuals with gastrointestinal intolerance to oral bisphosphonates. Dosage: 5mg iv once a year.

Denosumab denosumab may have a role in patients who are intolerant of or unresponsive to other therapies and in those with impaired renal function

OTHERS: PTH CALCITONIN raloxifene

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