 Glucocorticoids  Excessive thyroid hormone  Diuretics: Furosemide  Cyclosporine, methotrexate, tacrolimus  Seizure medications: Phenytoin, phenobarbital  Psychotropic: Lithium,  Heparin

 Initial evaluation:  CBC  Ca, p, Cr  Alkaline phosphatase, aminotransferases  25-hydroxyvitamin D  TSH  24-hour urine for Ca and creatinine

 Osteoporosis diagnosed when a radiograph shows signs of demineralization or compression fractures of vertebral bodies.  Techniques for evaluating bone mass:  Dual-energy x-ray absorptiometry (DEXA)  Quantitative (CT) of spine.  Ultrasound

 All postmenopausal women < 65 yr who have one or more additional risk factors for osteoporosis  All women > 65 yr regardless of additional risk factors  To document reduced bone density in patients with vertebral abnormalities or osteopenia on radiographs  To diagnose low bone mass in glucocorticoid-treated individuals  To document low bone density in patients with asymptomatic primary or secondary hyperparathyroidism

Calcium:  Goals of therapy for osteoporosis reduce bone resorption and enhance bone formation.  Bone loss occurs when Ca intake and absorption insufficient to balance daily Ca losses.  In absence of kidney stones or an underlying disorder of Ca metabolism,Ca intakes safe.

 Calcium carbonate : contains 40% elemental Ca should be taken with meals because of poor absorption in achlorhydric patients in absence of food.

 Calcium citrate : contains 24% elemental Ca, better bioavailability and is more absorbed. absorbed well on an empty stomach in patients with achlorhydria.

 Milk  Yogurt  Orange juice (with Ca)  Cheese  Ice cream (1/2 cup)  Soy milk (1 cup)  Beans (1/2 cup cooked)  Dark,green vegetables (1/2 cup cooked)  Almonds  Orange (1 medium)  300 mg  250 mg  300 mg  195 to 335 mg  100 mg  300 mg  60 to 80 mg  50 to 135 mg  70 mg  60 mg

 Tamoxifen :  Estrogen antagonist that binds to estrogen receptor  Estrogen-agonist effects on bone  Small increase in bone density of spine over 2 years,  No effect on radial bone density  45% reduction at hip and 29% at spine fracture.

 Raloxifene :  FDA approved for prevention and treatment of osteoporosis  Estrogen agonist on bone  Antagonist effects on breast and uterus.  Increased BMD in lumbar spine by 2.4%, in hip by 2.4%, in total body 2%  Over 2-year, significant reduction in vertebral fractures

 a potent inhibitor of osteoclastmediated bone resorption.  Human and salmon calcitonin available  Salmon calcitonin commonly used because greater potency.  Parenteral calcitonin (100 IU SC or IM three times a week or daily)  Maintain bone density or produce a small increase in bone mass in spine

 Nasal spray calcitonin absorbed through nasal mucosa  Approximately 40% as potent as parenterally administered (50 to 100 IU of injectable calcitonin comparable with 200 IU of nasal spray calcitonin).  Nasal calcitonin (200 IU/day) increases spinal bone density  No effect on proximal femur bone mass;  36% reduction in vertebral fractures over 5 years.

 Adverse effects of parenteral calcitonin: nausea flushing local irritation at injection site  Calcitonin intranasally well tolerated  Rhinitis and nasal dryness and crusting potential side effects.  Calcitonin may beneficial analgesic response in presence of osteoporotic fractures.

 Alendronate (Fosamax) is FDA approved for prevention and treatment of osteoporosis.  Alendronate (10 mg/day) produces:  8.8% and 7.8% increase in bone density in spine and femoral trochanter  Alendronate (70 mg) most commonly used dose for treatment of osteoporosis.

 Adverse effects of bisphosphonates:  GI symptoms: stomach pain esophagitis  Myalgias and arthralgias,  Osteonecrosis of jaw  Subtrochanteric fractures

 Risedronate :  Increased bone mass  Reduced risk of new vertebral fractures  Significant reduction in risk of hip fracture  Approved for prevention and treatment of osteoporosis(35 mg once a week)  Risedronate well tolerated even in patients with mild GI symptoms.

 Ibandronate :  Approved for treatment and prevention of osteoporosis.  Vertebral fractures reduce about 50%.  150 mg/month  Intravenous ibandronate in a dose of 3 mg every 3 months

 Zoledronic acid approved for treatment and prevention of osteoporosis.  5 mg once a year by intravenous infusion,  Risk of vertebral fractures reduce 68%, hip fractures 40%

 Side effects: arthralgias and myalagias;  Patients should have serum Ca and 25-OHD levels monitored and replaced to NL levels before treatment.

 Denosumab (Prolia) : Monoclonal antibody that against RANKL Approved for treatment of osteoporosis. 60 mg subcutaneously every 6 months for 36 months Vertebral fractures reduce 68%, hip fractures 40%, Well tolerated, Adverse events: skin infection Before treatment Ca and 25-OHD should be checked and replaced if needed up to normal levels.

 PTH significantly increase bone mass in spine,  Fortéo approved for treatment of osteoporosis.  20 μg/day for 21 months.  Lumbar spine bone mass increased between 9% and 13%,  Hip bone mass increased slightly.

 Risk of new vertebral fractures reduce nearly 70%.  Fortéo is given daily injection.  Individual may experience headache, nausea, flushing with initiation of treatment, but these side effects become less severe after few weeks.

 PTH :  Stimulates new bone formation  Increases bone mass  Reduces new vertebral and nonvertebral fractures

 Subcutaneous injection daily for 18 to 24 months.  Other routes of administration: intranasal skin patch.

 Physiologic doses of vitamin D important to NL bone mineralization.  Individuals 50 years of age and older should take at least 600 to 1000 IU of vitamin D daily  Low vit D levels increase risk of bone loss and fracture.

 Low 25-OHD levels during the winter and spring associated with decreases in bone density.  Daily treatment with 700 IU of cholecalciferol and 500 mg of Ca carbonate reduced rate of bone loss in: femoral neck, spine, total body  Decreased incidence of nonvertebral fractures by 50%.  Patients require a vit D intake that in 25-OHD level of at least 30 ng/mL.

 Patients starting GC therapy at a dose equivalent to prednisone ≥5 mg/day for 3 mo or longer should:  Modify risk factors for osteoporosis (stop smoking, decrease alcohol consumption)  Start regular weight-bearing physical exercise  Initiate intake of Ca (total 1500 mg/day) and vit D( I U/day)  BMD to predict risk of fracture and bone loss  Initiate bisphosphonate therapy (alendronate 5 mg/day or 35 mg/wk, or risedronate 5 mg/day or 35 mg/wk)

 If T-score is < −1:  Risk factor modification including reducing risk of falls  Regular weight-bearing physical exercises  Ca and vit D supplementation  Bisphosphonate therapy (alendronate 10 mg/day or 70 mg/wk,or risedronate 5 mg/day or 35 mg/wk);  If bisphosphonates contraindicated or not tolerated, calcitonin as second-line agent, intravenous bisphosphonate (pamidronate or zolendronate), parathyroid hormone  Repeat BMD measurement annually or biannually