• Most common bone dz
• Major public health problem
• Leads to: low bone mass, deterioration of bone tissue, disruption of bone architecture, compromised bone strength, ↑ risk of fracture

• Risk factor for fractures similar to HTN being a risk for stroke
• Majority of fx occur in pts with low bone mass (osteopenia) rather than osteoporosis

Both sexes, all races, prevalence ↑ with age

• 10 million americans 
• additional 33.6 have low bone density at the hip
• 1 in 2 caucasian women , and 1 in 5 men will have osteoporosis related fx 
• less freq in blacks, but those who have it have the same risk factors

• most common: spine, proximal femur (hip), distal forearm (wrist) - where spongy bone is located
• may be followed by full recovery or chronic pain, disability and death
• Psychological symptoms like depression and loss of self esteem from pan, loss of mobility and lifestyle and cosmetic changes
• anxiety, fear, anger
• interpersonal strain

• 10-20% excess mortality in 1 year
• 2.5 fold increase in further fx
• 20 require long term nursing care
• only 40% fully regain pre fx level of independence

• Peak bone mass 18-25
• determined largely by genetics, but nutrition, endocrine status, physical activity and health contribute
• bone remodeling remains a healthy skeleton, bone loss occurs when balance is altered
• influenced by menopause and advancing age
• all post menopausal women and men >50yo should be evaluated clinically for osteoporosis
• BMD testing should be considered
• more risk factors = greater fx risk
• no warning signs prior to fx; dx not made in time to receive effective therapy

• Corticosteroids (> 5mg/d or prednisone or equivalent for > 3 months)
• Chemotherapy
• anticonvulsants 
• anticoagulants (heparin)
• Gonadotropin releasing hormone agents
• Cyclosporine A and tacrolimus
• lithium
• aromatase inhibitiors
• depo-medroxprogesterone (& other progesterone bc)
• barbiturates

• low Ca intake
• vit D indufficiency
• excess Vit A
• high Caffeine or salt intake
• Aluminum (in antacids)
• Alcohol (3+ drinks/d)
• inactive lifestyle
• smoking (active or passive)
• falling
• Thinness

• low testosterone levels in men
• androgen insensitivity
• hyperprolactinemis
• Turner's Klinefelter's syndromes
• Anorexia nervosa and bulimia
• panhypopituirarism
• athletic amenorrhea
• premature ovarian failure

• adrenal insufficiency
• DM
• Throxtoxicosis
• Cushing's syndrome
• hyperparathyroidism

• Celiac dz
• IBD (use of steroids)
• Primary biliary cirrhosis
• Gastric bypass
• malabsorption
• GI surgery
•  pancreatic Dz

• Ankylosing spondylitis
• lupus
• RA

• alcoholism
• emphysema
• muscular dystrophy
• amyloidosis
• end stage renal dz
• parenteral nutrition
• chronic metabolic acidosis
• epilepsy
• post transplant bone dz
• CHF
• idiopathic scoliosis
• prior fx as adult
• depression 
• MS
• Sarcoidosis

• Most fx fall related, important ot evaluate for falling risk
  • personal hx of fall
  • muscle weakness
  • gait
  • balace 
  • visual deficits

BMD

• Grams of mineral per square centimeter scanned 
• Two comparisons can be made: 
  • T score (more often used)
  • Z score
• The difference between the pts score and the norm is expressed in standard deviations (SD) above or below the mean.
• Usually, 1 SD = 10-15% of the BMD value in g/cm²
• Spine, hips & wrist often measured, highest SD is used
• BMD shown to correlate w/ bone strength and is an excellent predictor of future fx risk

• Pts BMD is compared to "young normal" adults of the same sex 
• this is the comparison most often used

• BMD is between 1.0 and 2.5 SD below that of a "young normal" adult 
• T score between -1.0 and -2.5

• BMD is 2.5 SD or more below that of a "young normal" adult
• T score at or below -2.5
• pts in this group who have already experienced 1 or more fx are deemed to have severe or established osteoporosis

• Women 65+ & men 70+, regardless of clinical risk factors
• younger postmenopausal women and men (50-69), if ↑ risk factors (ie fx after age 50)
• women in menopausal transition if there are specific risk factors (low body wt, prior low trauma fx, meds)
• adult with a condition or taking meds that ↓ BMD
• anyone being considered for drug therapy for osteoporosis
• anyone being treated for osteoporosis, to monitor tmt effect
• postmenopausal women d/c estrogen

• can be measured in serum and urine in untreated pts to asses risk of fx (esp useful in perimenopausal women to determine risk of developing osteoporosis.
• may predict bone loss, and when repeated after 3-6 months of tmt, may be predictive of fx risk reduction
• Resorption markers: serum C-telopeptide (CTX), urinary N-telopeptide (NTX)
• Formation markers: serum bone specific alkaline phosphatase (BSAP) & osteocalcin

• Us fx risk algorithm
• developed to calculate the 10 yr probability of a hip fx and the 10 year probability of a major osteoporotic fx
• Used for consideration of tmt: low bone mass (Tscore between -1.0 and -2.5 at femoral neck or spine) 

1. current age

2. RA

3. Gender

4. 2° osteoporosis

5. prior osteoporotic fx

6. parental hx of hip fx

7. femoral neck BMD

8. Current smoking

9. low body mass index (Kg/m²)

10. alcohol intake 3+ drinks/d

11. oral glucocorticoid > 5 mg/d of prednisone for > 3 months ever

• bone becomes more porous 
• architecturally weakened structure/ reduced mass

• lifestyle modifications
  • Adequate Calcium and Vitamin D
  • Regular wt bearing exercise (consider PT)
  • fall prevention (consider OT)
  • smoking cessation
  • avoid excess alcohol

• Premenopausal Women and Med: 1000mg qd
• Post menopausal women (not on estrogen): 1500 mg qd
• >2000 mg qd not recommended d/t side effects
• Divide doses: 500mg/dose
• Calcium carbonate: effective, least expensive, not absorbed well with PPIs or H2 blockers
• Calcium Citrate: absorbed best with empty stomach
• Natural calcium carbonate preparations (ie oyster shells): often not regulated 

• All adults should consume at least 800-1000 IU/d (considered my many to be an insufficient amount)
• up to 75% of individuals are vit D deficient
• safe upper limit 2000 iu/d established in 1997

• detailed Hx for risk factors
• PE to evaluate for osteoporosis and its 2° causes
• Modify diet/supplements and other risk facotrs
• Estimate FRAX 
• Determine if medical or non medical therapies are needed
  • medical therapy not needed: clinically re-evaluate when medically appropriate (usually 2 years)
  • Medical therapy needed: labs and bone density re-evaluated after 2 years or more frequently when medically appropriate

• vertebral or hip fx
• DXA hip or spine Tscore < or = -2.5
• low bone mass and a FRAX > or = 20%
• pt preferences may indicate tmt for people with 10 year fx probabilities above or below these levels

• Bisphosphonates (Boniva, reclast, Actonel, Fosamax)
• Estrogen replacement therapy (ESR/HRT)
• Calcitonin
• SERMS
• Teriparatide Forteo
• Atelvia
• Prolia

- Most widely prescribed class of drugs for prevention and tmt of osteoporosis

- give largest gain in bone density

- proven to ↓ fx at the spine and other sites

- Side effects: GI intolerance

- take on empty stomach for max effect

- pt should then remain upright for 30 minutes/ 60 for ibandronate

- Actonel, Fosamax, Boniva, Reclast

Mech of bisphosphonates

• Antiresorptive therapy
• Ingested by osteoclasts & decreases the breakdown of bone
• non nitrogenous and nitrogenous forms
• used for: osteoporosis, Pagent's dz, bone metastasis, multiple myeloma

• A bisphosphonate used for prevention/tmt/steroid induced/men. Dosage 150mg once a month
• 41-49% reduction in new vertebral fx over 3 years
• 39% cumulative ↓ of nonvertebral fx over 3 years 
• 40-60% ↓ hip fx
• statistically sig ↑ in BMD seen within 6 months
• ↓ in bone turnover markers of premenopausal states

• A bisphosphonate used for prevention/tmt/steroid induced
• 50% ↓ in fx at vertebral and non vertebral sites
• ↓ biochemical bone turnover markers by 70%
  
• Bone density ↑ as early as 3 months
• sig ↑ bone mineral density over 10 years
• Cheaper generic form now available, not coated so more GI issues

• Ibandronate
• A bisphosphonate used for prevention/tmt
• 52% reduction in vertebral fx in 3 years
• stat sig ↑ in BMD as early as 6 months hip and spine
• no clinical data showing ↓ of non vertebras fx including hip

Boniva

Reclast

• administered IV over 15-30 seconds
• IV admin eliminates the need for pre and post dose fasting and activity restrictions
• Given every 3 months
• BMD builds similar to oral

• Zolendronic acid
• A bisphosphonate used for prevention/tmt/steroid induced/men
• Risk reduction at 3 years: 71% at spine; 41% hip; 25% non vertebral
• 5mg/100ml aqueous solution infused over 15 min once yearly
• acute phase reaction (arthralgia, headache, myalgia, fever): occur in 32% of pts after 1st dose, 7% after 2nd dose and 3% after 3rd dose
• higher risk of deveoloping a fib vs placebo (0.4:1.3) risk of other bisphosphonates is uncertain

Estrogen replacement therapy

• WHO found 34% ↓ in hip fx and 23% ↓ other fx when pt on ERT/HRT
• recommended for short-term control of vasomotor symptoms, vaginal dryness and urinary symptoms in menopause
• Should not be used to ↓ risk of osteoporosis if it is the only indication for its use

• Salmon calcitonin: synthetic hormone for tmt of postmenopausal osteoporosis in women at least 5 years post menopausal
• slows bone lose, ↑BMD, ↓ fx risk
• reported ot give some pain relief from osteoporotic fx
• injectable and nasal spray forms
• Side effects include: flushing, nausea, stomach upset (injectible form); itchy or runny nose (nasal spray)
• both forms 1/day
• 33% ↓ in vertebral fx with 200 iu, no sig ↓ in hip or nonvertebral fx with 200 iw
• stat sig ↑ in lumbar spine BMD
• Major adverse event was rhinitis

• Raloxifene/Evista
• for prevention and tmt
• Have estrogen like effects
• prevents bone loss, reduces total and LDL cholesterol
• does not stimulate uterine or breast tissue
• most common side effects: hot flashes
• Possible side effects: increased risk of thrombosis
• Pill form 1/day

• A SERM
• shows 30% ↓ in vertebral fx at 36 months in women with prior fx; 55% in those without prior fx
• no stat sig ↓ in nonvertebral fxs
• contraindication in women who are premenopausal, must be 6 months postmenopausal; contraindicated  in pregnancy
• 60mg/d with or without food

• Used for tmt of osteoporosis in postmenopausal women and men at high risk for fx, as well as risk of steroid induced osteoporosis
• anabolic (bone building) agent administered via daily sc injection
• 20ug daily shown to ↓ risk of vertebral fx by 65% and non vertebral fx by 53% after an average of 18 mths
• Contraindications: pts at ↑ risk of osteosarcoma (ie Pagent's dz), prior radiation of the skeleton, bone metastases or hypercalcemia
• Do not give longer than 2 years
• Common to follow tmt with antiresorptive agent, usually bisphosphonate to maintain further ↑ BMD

• New product for postmenopausal osteoporosis at high risk of fx
• (60mg sc every 6 months)
• Rank Ligand inhibitor, blocks formation fxn and survival of osteoclasts, totally new class
• safety issues: greater risk of serious infection, dermatologic adverse rxns, osteonecrosis, suppression of bone turnover, possible ↑ CA

• new product for tmt of postmenopausal osteoporosis
• Risedronate is a delayed release formulation
• Equivalent BMD increases to 5mg Actonel qd
• 35mg qam with food/ immediately following breakfast with 4 oz of water
  • will ↓ GI problems and ↑ compliance

DXA: gold standard

- every 2 years; NOF recommends; MCARE pays

Bone turnover markers:

- suppression of biochemical markers of bone turnover after 3-6 months of specific antiresorptive therapy, and biochemical marker ↑ after 1-3 months of specific anabolic therapy, have been predictive of greater BMD responses 

- early morning or overnight fast; serial measurements at the same time of day