Understanding Osteoporosis Diagnosis and Prevention

DEFINITIONS Osteoporosis A clinical diagnosis of osteoporosis may be made in the presence of a fragility fracture , particularly at the spine , hip , wrist , humerus , rib, pelvis, without measurement of (BMD).

Fragility fractures are those occurring from a fall from a standing height or less, without major trauma such as a motor vehicle accident Fractures at some skeletal sites, including the skull, cervical spine hands Feet are not considered to be fragility fractures.

In the absence of a fragility fracture , BMD assessment by dual-energy x-ray absorptiometry (DXA) is the gold standard to diagnose osteoporosis,

osteoporosis BMD that is 2.5 standard deviations (SDs) or more below the mean BMD of a young-adult reference population , which is a T-score of -2.5 or less, qualifies for a diagnosis of osteoporosis

Low bone mass Low bone mass (osteopenia) is defined as a T-score between -1.0 to -2.5

MAXIMIZING PEAK BONE MASS All children, and in particular, adolescents, should have adequate calcium and vitamin D intake engage in regular physical activity, achieve normal body weight, and avoid smoking and alcohol use Children 9 to 18 years of age should consume approximately 1300 mg of calcium daily , preferably from calcium-rich or calcium-fortified foods . Adequate vitamin D (600 international units) is necessary to promote intestinal calcium absorption

peak bone mass The timing of peak bone mass is not known with certainty but probably occurs in the third decade of life in most individuals Environmental factors include diet, exercise, habits (smoking, alcohol use), diseases, and medications.

Physical activity beneficial effects of exercise on bone accumulation during growth, with particular benefit from high-impact exercise excessive exercise can be harmful to skeletal health when it is accompanied by poor nutrition and reduced body fat,

Other lifestyle factors Cigarette smoking and excess alcohol intake should be discouraged glucocorticoids and anticonvulsants, should be avoided or minimized in dose and duration

Pharmacologic therapy There is no role for pharmacologic therapy as a means to maximize peak bone mass, pharmacologic doses of vitamin D for some children on anticonvulsant therapy or with celiac disease may be necessary to optimize skeletal health physiologic hormone replacement for deficiency states in children, such as growth hormone deficiency or hypogonadotropic hypogonadism, is essential to achieve normal peak bone mass

pyramid approach to the prevention and treatment of osteoporosis with a foundation of lifestyle changes that include Nutrition , physical activity , and fall prevention second tier of addressing drugs and diseases associated with bone loss or osteoporosis third tier of pharmacologic therapy

In men under age 50 years there was a slow rate of bone loss at the hip, but not the spine, that continued throughout life Age-related bone loss in older women and men is approximately 0.5 to 1.0 percent per year.

Factors that influence the rate and magnitude of bone loss include concomitant diseases , hormone concentrations , age , body weight , calcium and vitamin D intake , physical activity , family history , alcohol consumption cigarette smoking.

Calcium and vitamin D daily for most postmenopausal women 800 international units of vitamin D daily and 1200 mg elemental calcium (ideally from diet, plus supplements if needed)

dietary allowance of vitamin D for children 1 to 18 years and adults through age 70 years is 600 international units and 800 international units (20 mcg) after age 71 years

osteoporosis in a premenopausal woman The guidelines for the treatment of osteoporosis based on(BMD) in postmenopausal women do not generally apply to premenopausal women, as the relationship between bone mass and fracture in premenopausal women is not the same as in postmenopausal women

SCREENING Bone density screening is not routinely recommended for premenopausal women

BMD screening for premenopausal women under the following circumstances History of a fragility fracture Known secondary causes of osteoporosis

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) Hypercalciuria Rheumatoid arthritis and other inflammatory conditions Alcoholism Renal disease Liver disease

Initial evaluation Premenopausal women who come to medical attention in the setting of a fragility fracture or after learning of low (BMD; Z-score -2.0) should have an evaluation to identify potential secondary causes.

Laboratory evaluation may help to diagnose secondary causes of osteoporosis , such as renal or liver disease, hyperthyroidism, hyperparathyroidism, Cushing's syndrome or subclinical hypercortisolism, early menopause, celiac disease and other forms of malabsorption, idiopathic hypercalciuria, , connective tissue disorders.

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) 24-hour urine for calcium and creatinine

should be tested for celiac disease. Women with anemia , low urinary calcium excretion , and/or low vitamin D levels

Serum (PTH) and 1,25-dihydroxyvitamin D should be measured in patients with hypercalcemia , hypercalciuria , or a history of renal stone

Urinary cortisol excretion should be measured if Cushing's syndrome is suspected and also in patients with unexplained osteoporotic fracture, since patients with subclinical hypercortisolism (mild hypercortisolism without clinical manifestations of Cushing's syndrome) are at risk for low BMD and fractures.

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 (medications, poor nutrition, estrogen deficiency) that occurred during adolescence and are no longer present at the time of evaluation.

idiopathic osteoporosis Premenopausal women with bone fragility and no identifiable etiology after extensive evaluation for secondary causes are said to have idiopathic osteoporosis.

treatment with medications in premenopausal women is usually reserved for those with fracture(s) , active bone loss, and/or known ongoing secondary causes of osteoporosis and bone loss.

Fractures or accelerated bone loss Women with fractures or accelerated bone loss in the setting of hypogonadism may benefit from estrogen replacement

In women with normal gonadal function or in those who cannot take estrogen bisphosphonates and teriparatide are generally the drugs of choice in the rare cases when pharmacologic therapy is indicated fragility fractures accelerated bone loss [approximately 4 percent/year, depending on clinical setting]).

Without fractures or accelerated bone loss premenopausal women with low (BMD) alone without fractures known secondary causes for low BMD or evidence of accelerated bone loss , pharmacotherapy is almost never indicated

Management of premenopausal osteoporosis Calcium 1000 mg daily Vitamin D 600 international units daily Weightbearing exercise Changes in habits (avoidance of smoking, excess alcohol, poor nutrition) Treatment of secondary causes Pharmacologic treatment in selected cases

there is a history of nephrolithiasis additional evaluation (such as measurement of PTH and 1,25 dihydroxyvitamin D levels) is required before making supplementation recommendations.

Intensity of exercise enjoyment of the regimen is important (the benefits of exercise are quickly lost after its cessation) Excessive exercise in premenopausal women may lead to weight loss and/or hypothalamic amenorrhea, exacerbating low bone density

Pharmacologic therapies Estrogen In women with hypogonadism from various causes, treatment should be directed at the underlying cause. If resumption of menses is unlikely , estrogen therapy is usually the treatment of choice.

the long half-life of bisphosphonates in bone suggest that use of these agents in reproductive-age women should be limited to special circumstances

Parathyroid hormone analogs has been used successfully in clinical trials to prevent bone loss in premenopausal women on (GnRH) agonists for the treatment of endometriosis in premenopausal women taking glucocorticoids in premenopausal women with idiopathic osteoporosis in women with pregnancy and lactation-associated osteoporosis and in those with AN

Parathyroid hormone analogs Use of this medication should be avoided in those at increased risk of osteosarcoma including those with Paget disease , prior radiation , growing bones [open epiphyses] , or unexplained elevation in alkaline phosphatase

Parathyroid hormone analogs this medication should be used with great caution in young women and use should be avoided in those with delayed growth or open epiphyses.

SERMs SERMs such as raloxifene and tamoxifen should not be used to treat osteoporosis in menstruating women, as they block estrogen action on bone leading to further bone loss

Calcitonin Is available in the United States for administration by the subcutaneous, intramuscular, and intranasal routes The bioavailability of nasal salmon calcitonin is approximately 25 percent that of intramuscular calcitonin; thus, the biological effect of 50 international units of intramuscular salmon calcitonin is equivalent to that of 200 international units of nasal salmon calcitonin The absorption of the nasal dose is delayed compared with the parenteral route

The administration of salmon calcitonin is frequently associated with side effects such as nausea , vomiting Flushing ; these side effects are much less common with the nasal route

Nasal salmon calcitonin may provide more effective analgesia than parenteral salmon calcitonin nasal salmon calcitonin the preferred route of administration in patients who can tolerate and cooperate with intranasal administration

Osteoporosis treatment Calcitonin may be effective in the treatment of established osteoporosis, but it is less effective than other available agents

Bone pain Calcitonin has a beneficial short-term effect on acute pain relief in patients who have sustained a vertebral fracture, In contrast, calcitonin was not effective for patients with chronic pain. nasal calcitonin relieved pain more effectively than parenteral calcitonin

Other adverse effects of calcitonin hypersensitivity reactions (bronchospasm, swelling of the tongue or throat, anaphylaxis), hypocalcemia , nasal adverse reactions (rhinitis, epistaxis) , and the formation of antibodies to calcitonin In clinical trials of nasal calcitonin in postmenopausal women, the most common adverse effects were rhinitis and epistaxis, occurring in 12 and 4 percent, respectively.

Denosumab Although denosumab may have some advantages in premenopausal populations because of its shorter half-life relative to bisphosphonates and lack of skeletal accumulation, the efficacy and safety of this medication have not been defined in premenopausal women Denosumab, as marketed for osteoporosis, has been assigned a designation of pregnancy category X

High risk for ongoing bone loss or fracture Glucocorticoids calcium and vitamin D supplementation combination estrogen-progestin contraception (if not contraindicated) in premenopausal women with amenorrhea who are initiating or taking glucocorticoids Glucocorticoids reduce the production of sex steroids

Moderate to high fracture risk includes women with prior osteoporotic fracture, as well as women with very low BMD (Z-score <-3) or with very rapid bone loss who are continuing glucocorticoid treatment at 7.5 mg of prednisone or equivalent per day for 6 months. Treatment with oral bisphosphonates or teriparatide are preferred in this population and in the setting of use of effective contraception