Paget's/OP Flashcards
What is the typical clinical presentation of Paget’s?
- Often no symptoms
- May be incidental finding on imaging or inc ALP
- If you have symptoms the most common is pain (persistent, sleeping)
- Can also have OA, nerve impingement
- Deformities = bowing of lower limbs
- Fractures = complete (transverse) or fissure, long bone
- Warm skin over area
- Steal syndrome = hypervascularity of bone so adjacent gets ischemic, intermittent claudication
- Neurologic = HA, spinal stenosis, hearing loss
- Neoplastic transformation = osteosarcoma, giant cell tumours
Indications for tx of Paget’s
- Symptomatic disease
- Asymptomatic - location risk for future complications, and signs of active disease with inc ALP or bone scintigraphy)
- Surgery planned at active site
- Hypercalcemia in setting of immobilization
Treatment for Paget’s
Zoledronic acid - 5 mg, single 15 min IV infusion
Risedronate - 30 mg/day x 2 months (less effective)
Alendronate 40 mg/day x 6 months
Calcitonin if intolerant of bisphosphonates
Denosumab - may be good in renally impaired, not great data
What marker should be followed during tx for Paget’s?
ALP
Measure no earlier than 3 mos after start tx, ideal 6 mos
Check ALP q3 mos for first 6 mos the annually
Complications of Paget’s
Neurologic: nerve root compression, CN entrapment, deafness, spinal stenosis, vascular steal syndrome
Orthopaedic: secondary OA, pathologic #, bone deformity, inc bleeding in surgery
Oncologic: osteosarcoma, giant cell tumors
Metabolic: secondary hyperPTH, hyperCa, hypercalciuria
Goals of treatment in Paget’s
Serum ALP normal
Resolution of symptoms
Radiographic improvement
What is the cause of Paget’s?
Familial and sporadic forms
Viral cause
How is Paget’s diagnosed?
Radiologic - characteristic deformity of bone, thickened cortices, tunnelling and accentuated trabeculae
Baseline radionuclide bone scan in all patients (extent, location)
XR other areas if found
What are the main classes of treatment options for osteoporosis?
- Bisphosphonate (alendronate, risedronate, ZA)
- RANKL inhibitor (denosumab)
- PTH analogue (Teriparatide)
- SERM (raloxifene)
- Anti-sclerostin antibodies (romosozumab)
Bisphosphonate mechanism and side effect
Mechanism: taken up by osteoclasts during bone resorption inhibiting OC resorptive ability and triggering apoptosis
SFx: upper GI, MSK discomfort, ZA - flu like, hypoCa
Rare: ONJ, AFF
Denosumab mechanism and side effect
Mechanism: monoclonal Ab that binds to RANKL, prevents it from binding to RANK which prevents OC maturation
SFx: MSK discomfort, hypoCa, dermatitis/infection
Rare: oNJ, AFF
Teriparatide mechanism and side effect
Mechanism: PTH analogue that activates PTH R = inc activity of OB and OC = overall net bone gain
SFx: MSK discomfort, hyperCa, hypercalciuria, nausea, orthostatic HOTN
Raloxifene mechanism and side effect
Mechanism: SERM, binds to estrogen R, provides mixed antagonist-agonist effect, weak anti resorptive effects to reduce risk of vertebral #
SFx: thromboembolic, CVD, stroke, vasomotor, leg cramps
Romosozumab mechanism and side effect
Mechanism: anti sclerotin antibody, sclerotin inhibits OBs, Ab stimulates formation and inhibits resorption due to effects on osteoprotegerin levels
SFx: MI, stroke, hypoCa, muscle discomfort
Rare: ONJ, AFF
5 ways romosozumab increases bone mineralization
Inc OB differentiation from mesenchymal stem cells
Reduces OB apoptosis
Inc bone matrix formation
Downregulates RANKL production (dec OC formation and bone resorption)
Upregulates OPG production (binds and opposes RANKL)
Increases BMD of L spine and total hip
5 management strategies for dx of vertebral fracture
- Pain control: oral (acetaminophen, ibuprofen, naproxen), opioid if 1-2 wks of inadequate analgesia (IR, lowest dose)
- Activity/early mobility - ASAP, complete bed rest not recommended
- PT - gait and core strengthening
- Bone density - OP defining fracture, baseline BMD, start OP therapy
- Vertebral augmentation - vertebroplasty or kyphoplasty (only if debilitating pain or substantial functional limits after min 3 weeks therapy)
Clinical Frailty Scale
1 - Very fit (robust, regularly exercise)
2 - Fit (no active disease sx, active seasonally)
3 - Managing well (med probs well controlled, not regularly active beyond walking)
4 - Very mild frailty (symptoms limit activity)
5 - Mild frailty (need help with higher IADLs)
6 - Mod frailty (help all outside activities, keeping house, maybe bathing/dressing)
7 - Severe frailty (completely dependent for personal care)
8 - Very severe frailty (completely dependent, approaching end of life)
9 - Terminally ill (life expectancy <6 mos, not otherwise living with severe frailty)
Risk of discontinuing denosumab
Sudden discontinuation comes with risk of vertebral fractures due to rapid increase in bone turnover (OC activity) and subsequent bone loss
Most bone loss in 12 mos
Switch to alternative antiresorptive and closely monitor for min 12 mos
Imaging findings of atypical femoral fracture
Location: femoral diaphysis
Cortical (endosteal/periosteal) thickening
Must involve lateral cortex
Mainly transverse (medially may be oblique)
No or minimal comminution
Management of AFF
- Stop bisphosphonate
- Consult ortho - surgery with intramedullary nail if complete #, disabling pain, or incomplete not improved by 2-3 mos
- Ensure adequate vit D and Ca
- Consider teriparatide (don’t change to denosumab if on bisphosphonate)
- Image contralateral femur
Risk factors for osteoporosis (11)
- Age 50+ yo
- Post menopausal F>M
- Fragility fracture after 40 (low trauma, craniofacial, hands and feet no)
- 2+ falls in last year
- Either parent with hip fracture
- BMI <20
- Current smoker
- Alcohol 3+ drinks per day
- > 3 mos steroids in last year (pred equivalent >5 mg daily)
- Secondary osteoporosis
- Vertebral compression #
Causes of secondary osteoporosis
- Drugs - steroids, chemo, anticonvulsants, aromatase inh
- Endocrine - hyperTSH, hyperPTH, DM
- GI - IBD, celiac, bariatric surgery
- Rheum - RA, SLE
- Genetic - OI, hypoPO4
- Other - MM, CKD, COPD, MS, Parkinson’s, Paget’s
Signs of possible vertebral fracture
Prospective height loss >2 cm, or historical <6 cm
Rib to pelvis <= 2 finger breadths, midaxillary
Occiput to wall >5 cm
Osteoporosis dx and tx flow chart
M and F >50
Recommend balance and muscle strength exercises 2+x/week
Suggest foods rich in Ca and protein
Suggest min Vit D 400 U/day
Assess for risk factors or undx vert #
Age <70 and no risk factors = above recs
Previous hip or spine # or 2+ # = auto high risk, recommend tx
Age 50-64 prev # or 2+ RFs, 65-69 with 1 RF, 70+ no RF = obtain BMD, calculate 10 yr risk (FRAX/CAROC)
10 yr risk <15% or T >-2.5 = NO tx
10 yr risk 15-19.9% or T<= -2.5 and <70 = suggest tx
10 yr risk 20%+ or T<=-2.5 and 70+ = recommend tx
Guidelines to reassess BMD/risk
If started tx = RA in 3 years
If not candidate or chose no tx
- 10 yr <10% = 5-10 yrs
- 10 yr 10-15% = 5 yrs
- 10 yr 15%+ = 3 yrs
SCOOP Trial results
Screening women age 70-85 with FRAX, BMD and suggest tx if high risk
Primary outcome = # participants with 1+ OP # at 5 yrs = no sig change
Secondary outcome = # participants with 1+ hip fracture, any clinical fracture or mortality = only hip fracture had 28% RRR
Outcomes used in osteoporosis trials
- BMD
- OP related fractures (all, hip, vertebral)
- Mortality
- Anxiety
- QOL
- Medication adherence
- ADRs
6 factors to consider for prescribing denosumab
- Able to take it on time q6 mos
- No AFF, ONJ (thigh/groin pain, poor dental health, invasive dental surgery, steroid use)
- Adequate vitamin D level (50+)
- Adequate Ca intake
- Assess for renal impairment (caution CrCl<30)
- Repeat BMD after 3 years unless secondary causes, new # or new clinical risk associated with rapid bone loss
Define inadequate response and what to do
Inadequate response >1 fracture or 5+% BMD decline despite adherence to adequate course (>1 yr)
If inadequate response: extend OR switch therapy, reassess 2ndary causes, seek advice expert
Duration of therapy bisphosphonates
Initial tx 3-6 yr
6 yr if hx of hip, vertebral or multiple nonvert #
OR if new/ongoing risk factors for accelerated bone loss/fracture
Stop therapy (drug holiday) then R/A 3 yr after (may be earlier for some)
Duration of therapy denosumab
Long term uninterrupted
When stopping transition to alternative
Duration of anabolic therapy (teriparatide, romo)
Teriparatide has a black box warning for use only for 2 years
Romo only for 1 year
Antiresorptive after anabolic
Lab investigations for secondary causes OP
Ca (correct albumin)
PO4
Cr
ALP
TSH
SPEP
25-hydroxy Vit D
3 clinical indications, 3 medical conditions and 3 risks to IV bisphosphonates
Indications
1. Can’t tolerate PO (sfx)
2. Can’t remain upright 30-60 mins after
3. Can’t swallow pill
Medical indications
1. Paget’s
2. HyperCa malignancy
3. Multiple myeloma
Risks
1. HypoCa (tx vit D def before start)
2. Acute renal failure (measure Cr before, hydrated, infuse over min 15 mins)
3. Flu like sx (longer infusion 45-60 mins, take Tyl/Advil)
Components of FRAX score
- Age 40-90 yrs
- Sex
- Weight kg
- Height cm
- Previous fragility fracture
- Parent hip fracture
- Current smoking
- Steroids (>3 mos in last year at >5 mg per day)
- RA
- Secondary OP
- Alcohol 3+ units/day
- Femoral neck BMD
Non-pharm recommendations for OP
Exercise
1. Balance and functional 2+/wk
2. Progressive resistance training 2+/wk
Nutrition
1. Ca RDA 1000 mg/d (M51-70), 1200 (F>50, M>70)
2. Vit D 600 IU/d (51-70) or 800 (>70)
At >50 supplement 400 IU daily
Risk deficiency then supply more
What type of fractures is each form of tx good for?
Bisphosphonates - all (vert, non vert, hip)
Denosumab - all
Hormone therapy - all
Romosoxumab - all
Teriparatide - vert and non vert (NOT HIP)
Raloxifene - only vert
What is the evidence for estrogen in OP?
Reduced vertebral, hip and all fractures combined compared with placebo
SERM only for vertebral fractures
3 age associated changes that predispose to OP
Decreased estradiol (inc resorption)
Dec bone stem cells
Dec osteoblasts (less made and more apoptosis)
Inc activity osteoclasts
Dec vit D conc (dec cutaneous and intestinal absorption)
Dec dietary Ca absorption
Dec physical activity/mechanical loading
Side effects of Ca and vit D
Vitamin D - hyperCa, hyperCauria, renal calculi, vit D intoxication (N/V, anorexia, constipation, fatigue, polydipsia, confusion, weak)
Ca - constipation/bloating/gas, nausea, anorexia, HA, renal calculi, interfere absorption of other meds
5 risk factors for fracture in LTC
- Prior fracture of hip or spine
- More than 1 prior fracture
- Recent use of steroids and 1 prior fracture
- High risk/receiving OP tx before admission
Additional: Vertebral fracture on CXR
Fracture prevention in LTC
- Risk assessment on admission
- Vit D >800-2000 U/day
- Calcium 1200 mg/d (max 500 support)
- Exercise - balance, strength, functional
- Med review - limit polypharm
- Evaluate environmental hazards
- Manage incontinence
- Assistive devices
- Hip protectors if high risk fall and ambulatory
- Pharmacotherapy if high risk and life expectancy >1 yr
OP indications for therapy for vertebral fracture
If within last 2 years and body height loss of >40% OR >1 vert fracture talk to specialist re: teriparatide or romosozumab
Otherwise any therapy, bisphosphonate usually first line
What is future risk of fracture if previous fracture?
RR 1.96
What is kyphoplasty? 2 benefits, 2 CI
Inflatable bone tamps to create cavity then percutaneous injection of bone cement under image guidance into # vertebrae
Vertebroplasty just injects cement
2 benefits: short term improved pain, prevent recurrent pain, improve function
CI: # due to infection/solid tumor/vascular lesion, burst fracture with loss of integrity of post vertebral cortex
Osteomalacia causes
Soft bones from defective mineralization of osteoid
Causes
1. Vit D deficiency/resistance
2. Inadequate Ca intake
3. HypoPO4 (inc secretion)
4. CKD
5. Renal tubular acidosis
6. Mineralization inhibitors (bisphosphonates, aluminum, fluoride
7. Hypophosphatasia (genetic disease)
8. Defective bone matrix
Osteomalacia treatment
Tx underlying cause
Correct PO4, Ca, and vit D
Aim vit D >75 - 50 000 U PO weeky x 6-8 weeks then 800 U daily
Calcium 1200 mg/day target
Osteomalacia muscle biopsy
Type 2 muscle fibre atrophy
What are indications to start anabolic therapy?
- Recent (2 yr) severe vertebral fracture (body height loss of 40%)
OR - > 1 vertebral fracture and T score of <= -2.5
When should BMD screening be done?
- All 70+
- 65-69 if 1+ risk factor
- 50-64 if prev OP fracture or 2+ risk factors
Who should have vertebral imaging with spine radiograph?
PM females and males without known vertebral fractures who:
Age 65+ with T score <= -2.5
10 year MOF risk between 15-19.9%
