Osteoporosis by P.Harischandra 20 Oct 2015

1. Osteoporosis byP.Harischandra20 Oct 2015

2. Background • The problem • Osteoporosis is common • Over 50% of women and 30-45% of men over age 50 have osteopenia/osteoporosis • White woman over age 50: 50 % lifetime risk of osteoporotic fracture, 25% risk vertebral fracture, 15% risk of hip fracture • Man over age 60 has 25% risk osteoporotic fracture • 70% over age 80 have osteoporosis • Hip fractures are bad • 20% patients with hip fracture die within the year • 25-30% need placement in skilled nursing facility

3. Older patients have frequent admissions and increased length of stay, increasing possible points of contact • Patients from nursing facilities, those at greatest risk, may have little continuity • Discharge medications for patients going to skilled nursing facilities can have LARGE impact • Study: Only 6% of patients admitted with hip fracture to a tertiary care hospital were adequately treated for osteoporosis at discharge, only 12% at 5 years! • Another study: only 21% medicare beneficiaries with hip fracture had any prescription treatment; patients older than 74 and those with other comorbidities were least likely to receive treatment

4. What is Osteoporosis? • Loss in total mineralized bone • Disruption of normal balance of bone breakdown and build up • Osteoclasts: bone resorption, stimulated by PTH • Calcitonin: inhibits osteoclastic bone resorption • Major mechanisms: • Slow down of bone build up: osteoporosis seen in older women and men (men after age 70) • Accelerated bone breakdown: postmenopausal • Normal loss .5% per year after peak in 20s • Up to 5% loss/year during first 5 years after menopause

5. Osteoporosis means "porous bones," causes bones to become weak and brittle – so brittle that even mild stresses like bending over, lifting a vacuum cleaner or coughing can cause a fracture. In most cases, bones weaken when low levels of calcium, phosphorus and other minerals in the bones and results as low bone density. A common result of osteoporosis is fractures of the spine, hip or wrist. Although it's often thought of as a women's disease, osteoporosis also affects many men.

6. CAUSES The strength of the bones depends on their size and density; bone density depends in part on the amount of calcium, phosphorus and other minerals bones contain. When the bones contain fewer minerals than normal, they're less strong and eventually lose their internal supporting structure.

8. The process of bone remodeling Scientists have yet to learn all the reasons why this occurs, but the process involves how bone is made. Bone is continuously changing — new bone is made and old bone is broken down — a process called remodeling, or bone turnover. A full cycle of bone remodeling takes about 2-3 months. In young – the body makes new bone faster than it breaks down old bone, and the bone mass increases.

9. Reaches the peak bone mass in mid-30s. After that, bone remodeling continues, but loses slightly more than gain. At menopause, when estrogen levels drop, bone loss increases dramatically. Many factors contribute to bone loss, the leading cause in women is decreased estrogen production during menopause.

10. Defining Osteoporosis • “systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk” • True Definition: bone with lower density and higher fracture risk • WHO: utilizes Bone Mineral Density as definition (T score <-2.5); surrogate marker

11. What keeps bones healthy Regular exercise Adequate amounts of calcium Adequate amounts of vitamin D, which is very essential for absorbing calcium

13. RISK FACTORS Sex – Fractures from osteoporosis are about twice more in women than in men. Risk in women at menopause (45 yrs) that accelerates bone loss. Risk in men is greater than age 75. Age. The older, the higher risk of osteoporosis. Bones become weaker as ages. Race. Greatest risk – white or of Southeast Asian descent. Black and Hispanic men and women have a lower, but still significant, risk.

14. Family history. Osteoporosis runs in families. Parent or sibling with osteoporosis puts at greater risk, especially if having a family history of fractures. Frame size. Men and women who are exceptionally thin or have small body frames tend to have higher risk because they may have less bone mass to draw from as they age. Lifetime exposure to estrogen. The greater a woman's lifetime exposure to estrogen, the lower her risk of osteoporosis. Eating disorders. Women and men with anorexia nervosa or bulimia are at higher risk of lower bone density in their lower backs and hips. Corticosteroid medications. Long-term use like prednisone, cortisone, prednisolone and dexamethasone, is damaging to bone. Common treatments for chronic conditions – asthma, rheumatoid arthritis and psoriasis. Thyroid hormone. Too much thyroid hormone can cause bone loss.

15. Other medications. Long-term use of the blood-thinning medication heparin, the cancer treatment drug methotrexate, some anti-seizure medications, diuretics and aluminum-containing antacids also can cause bone loss. Breast cancer. Postmenopausal women who have had breast cancer are at increased risk of osteoporosis, especially if they were treated with chemotherapy or aromatase inhibitors such as anastrozole and letrozole, which suppress estrogen. Low calcium intake. A lifelong lack of calcium plays a major role in the development of osteoporosis. Medical conditions and procedures that decrease calcium absorption. Stomach surgery (gastrectomy) can affect the body's ability to absorb calcium.

16. Sedentary lifestyle. Bone health begins in childhood. Children who are physically active and consume adequate amounts of calcium-containing foods have the greatest bone density. Exercise throughout life is important, but can increase bone density at any age. Excess soda consumption. The link between osteoporosis and caffeinated sodas isn't clear, but caffeine may interfere with calcium absorption and its diuretic effect may increase mineral loss. In addition, the phosphoric acid in soda may contribute to bone loss by changing the acid balance in the blood. Chronic alcoholism. For men, alcoholism is one of the leading risk factors for osteoporosis. Excess consumption of alcohol reduces bone formation and interferes with the body's ability to absorb calcium. Depression. People who experience serious depression have increased rates of bone loss.

17. COMPLICATIONS Fractures are the most frequent and serious complication of osteoporosis. Often occurs in spine or hips – bones that directly support your weight. Hip fractures and wrist fractures from falls are common. Compression fractures can cause severe pain and require a long recovery. If many such fractures, can lose several inches of height as the posture becomes stooped.

18. TESTS AND DIAGNOSIS Osteopenia refers to mild bone loss that isn't severe enough to be called osteoporosis, but that increases the risk of osteoporosis. The best screening test is dual energy X-ray absorptiometry (DEXA) – measures the density of bones in the spine, hip and wrist and it's used to accurately follow changes in these bones over time. Ultrasound Quantitative CT scanning Dual energy X-ray absorptiometry

19. Diagnosing Osteoporosis • Laboratory Data • Limited value in diagnosis • Markers of bone turnover (telopeptide) more useful in monitoring effects of treatment than in diagnosis • Helpful to exclude secondary causes • Hyperthyroidism • Hyperparathyroidism • Estrogen or testosterone deficiency • Malignancy • Multiple myeloma • Calcium/Vitamin D deficiency

20. Methods to evaluate for osteoporosis • Quantitative Ultrasonography • Quantitative computed tomography • Dual Energy X-ray Absorptiometry (DEXA) • ?”gold standard” • Measurements vary by site • Heel and forearm: easy but less reliable (outcome of interest is fracture of vertebra or hip!) • Hip site: best correlation with future risk hip fracture • Vertebral spine: predict vertebral fractures; risk of falsely HIGH scores if underlying OA/osteophytes

21. How to interpret the BMD • T score: standard deviation of the BMD from the average sex matched 35-year-old • Z score: less used; standard deviation score compared to age matched controls • WHO: Osteoporosis: T score <-2.5 • Osteopenia: T score -1 - -2.5 • For every 1 decrease in T score, double risk of fracture • 1 SD decrease in BMD = 14 year increase in age for predicting hip fracture risk • Regardless of BMD, patients with prior osteoporotic fracture have up to 5 times risk of future fracture!

22. Fracture Reduction • Goal: prevent fracture, not just treat BMD • Osteoporosis treatment options • Calcium and vitamin D • Calcitonin • Bisphosphonates • Estrogen replacement • Selective Estrogen Receptor Modulators • Parathyroid Hormone

23. TREATMENTS AND DRUGS Hormone therapy (HT) Prescription medications – Bisphosphonates, Raloxifene (Evista) / selective estrogen receptor modulators (SERMs), Calcitonin, Teriparatide (Forteo), Tamoxifen. Emerging therapies – New physical therapy program combines the use of a device called a spinal weighted kypho-orthosis (WKO), a harness with a light weight attached and specific back extension exercises. The WKO is worn daily for 30 minutes in the morning and afternoon.

24. Osteoporosis Treatment: Calcium and Vitamin D • Fewer than half adults take recommended amounts • Higher risk: malabsorption, renal disease, liver disease • Calcium and vit D supplementation shown to decrease risk of hip fracture in older adults • 1000 mg/day standard; 1500 mg/day in postmenopausal women/osteoporosis • Vitamin D (25 and 1,25): 400 IU day at least; • Frail older patients with limited sun exposure may need up to 800 IU/day

25. Osteoporosis Treatment: Calcitonin • Likely not as effective as bisphosphonates • 200 IU nasally/day (alternating nares) • Decrease pain with acute vertebral compression fracture

26. Osteoporosis Treatment: Bisphosphonates • Decrease bone resorption • Multiple studies demonstrate decrease in hip and vertebral fractures • Alendronate, risodronate • IV: pamidronate, zolendronate (usually used for hypercalcemia of malignancy, malignancy related fractures, and multiple myeloma related osteopenia) • Ibandronate (boniva): once/month • Those at highest risk of fracture (pre-existing vertebral fractures) had greatest benefit with treatment

27. Bisphosphonate Associated Osteonecrosis (BON) • Jaw osteonecrosis • Underlying significant dental disease • Usually associated with IV formulations • Case reports associated with oral formulations

28. Bisphosphonates: Contraindications • Renal failure • Esophageal erosions • GERD, benign strictures, most benign GI problems are NOT a contraindication • Concern for esophageal irritation/erosions from direct irritation, recommendations to drink water after and not lie down at least 30 minutes • Reality: no increased GI side effects compared to placebo group in multiple studies

29. ESTROGEN AND BONE PROTECTION Estrogen is essential for healthy bone, and that when the production of estrogen is reduced, as occurs normally in postmenopausal women and pathogenically after exposure to radiation or chemotherapeutic drugs, bones become brittle and break easily. However, the mechanisms involved aren't clearly understood.

30. Osteoporosis Treatment: Estrogen Replacement • Reduction in bone resorption • Proven benefits in treatment • FDA approval, now limited because of recent concerns from HERS trial and other data suggesting possible increased total risks with HRT (?increased cardiac risk, increased risk VTE, increased risk cancer)

31. Osteoporosis Treatment: Selective Estrogen Receptor Modulators • Raloxifene • FDA recommended • Decrease bone resorption like estrogen • No increased risk cancer (decrease risk breast cancer) • Increase in vasomotor symptoms associated with menopause

32. Osteoporosis Treatment: PTH • Teriparatide • Why PTH when well known association with hyperparathyroidism and osteoporosis??? • INTERMITTENT PTH: overall improvement in bone density • Optimal bone strength relies upon balance between bone breakdown and bone build up; studies with increased density but increased fracture risk/fragility with flouride show that just building up bone is not enough!!!

33. Intermittent PTH: Teriparatide • Studies suggest improved BMD and decreased fractures • ?risk osteosarcoma with prolonged use (over 2 years): studies with rats • SQ, expensive • Option for severe osteoporosis, those on bisphophonates for 7-10 years, those who can not tolerate oral bisphosphonate • Optimal effect requires bone uptake • Not for use in combination with Bisphosphonate! • May need to stop bisphosphonate up to 1 year prior

34. Reducing Fractures • 1. Decrease osteoporosis/improve BMD • 2. Decrease risk of break: hip protectors • 3. Decrease risk of fall

35. Hip Protectors • Padding that fits under clothing • Multiple studies demonstrate effectiveness at preventing hip fractures • Likely cost effective • Problem: adherence!

36. Falls Reduction • Falls are a marker of frailty • Hip fracture is a marker of frailty • Mortality after hip fracture:?due to hip fracture or hip fracture as marker for those who are declining? • Increased risk of falls: • Prior fall (fear of falling) • Cognitive decline • Loss of vision • Peripheral neuropathy • Weakness • Stroke • Medications: anticholinergics, tcas, benzos… • ETOH

37. Current Guidelines • US Preventive Task Force • Test Bone Mineral Density in all women over age 65, younger postmenopausal women with at least one risk factor, and postmenopausal women with a history of fracture • Treat patients with T score <-2 and no risk factors, T score <1.5 if any risk factors, and anyone with prior vertebral/hip fracture

39. Who is left out? • Older men • Not included in recommendations • Screening not recommended or paid for • Significant problem, risk of osteoporosis, risk of fracture, especially after age 70, even more so after age 80 • Significant evidence that men with osteoporosis benefit from treatment

40. References • Harrison’s Principles of Internal Medicine 19th edition • Davidson Principles and Practice of Medicine 23rd edition