Osteoporosis

Question 1

WHO Def of Osteoporisis

Answer 1

• Osteoporosis - T score -2.5
  
  • Reduce bone mass with increased risk of low trauma fractures (fragility fractures)
• Osteopenia - T score -1 to -2.5
• Normal - T score >/-1

A T score is an axial boen density T score measured by dual energy X ray absorptiometry (XA)

Question 2

Clinical RFs

Answer 2

• Advancign age
• Previous fracture
• Glucocorticoid therapy (GIO)
• FH of hip fracture
• Low body weight (bMI <20)
• Current cigarette smoking and excessive alcohol consumption (.3.5 unit/day)
• RA
• Secondary Osteoporosis (hypogonadism, premature menopause, malabsroption, chronic liver disease).

Question 3

What tool can you use for fracture risk assessments and the limitations

Answer 3

FRAX - WHO fracture risk assessment tool

• Looks at age, sex,w eight, height, previosu fractures, parent fractured hip, current smoking, clucocorticoids, RA, secondoanry osteoproisis, alcohol 3+ units day, alcohol 3more units per day., femoral neck BMD.
• Doesnt accomodate all known RFs, falls, biochemical markers
• Lacks detail on some RFs - dose repsonse effects of glucocorticoids, smoking, prior fracture
• Depends on adequacy of epidemiological info
• Model relevant only for untreated patients
• Not well validated in younger pop
• Only accounts for hip/NOF BMD

Qfracture - online fracture risks coring tool, developed in uk which can be used to rpedict absoloute risk of hip fracture and of maoe osteoporotic fractures (spine, wrist, hip, or hsoulder) over tiemframe sof 1-10years.

Question 4

Current medical treatment options in osteoporosis

Answer 4

• Calcium + vitamin D= 700mg/day (frail + older)
• Biphosphonates = reduce bone turnover. Increase bone density (decrease remodelling spacce) and increase secondary minerlaisation. Presvere bone structure. Harm vs benefit (continuining and stopping). Clea rbeenefit for 5years (do u stop after 5yrs if no vertebral fractures. Maybe 10yrs for those with vertebral fractures, bone markers threshold.
  
  • Effectiveness: more effecive ->least - IV Zoledronic acid, IV Ibandronic acid. Alendronate, risedronate, ibandronate, Etidronate
  • IV xoledronate 5mg annualt - nephrotoxicit, avoid if eGFR <35, ensure vit D replete
  • Aledronci acid - firts line (cost + nice), generic, for over 20y/o, reduced risk of vert, non-vert and hip fractures. Veyr limited data in >80 y/o, but up to 60% patients will stop treatment at 6months
  • Risedronate - Lower bone affinity, and less potent than alendronci acid. May enable greater access to osteocytes. Possibly explains similar efficacy to more potent antiresorptives. POss fewer GI side effects, preferred treatmetn for GIOP.
  • Ibandronate - month 150mg oral. Conveence + tolerability (GI), non inferiority head to head with alendornate (BMD). IV every 3months, no renal toxicity, second line oral phosphophonate
• Denosumab (Prolia) = Highly potent and rapidly acting antiresorptive (85% decrease in serum CTX after 3days). Human monoclonal Ab against RANK ligand (mimics osteoprotegrin). 60mg every 6m s/c. Liensed for R of PMO (increased risk fractures). Men with Ca prostate - treatmnt induced bone loss
  
  • Drug safety update MHRA 2012. Cases of severe symptomati hypocalcaemia so dont use 60mg in thos ewith hypocalcaemia, regardles severity. ASequate intake Ca and Vit D importan tin those receiving 60mg denosumab. patients with severe renal impairment eGFR 15-29 or dialsys are greater risk hypocalcaemia so monitor. Also rare cases astypical femoral fracture with long term se in postmenopausal so with paina round their evluate for fem frcture.
  • Pirmayr prevention in prveention osteoporotic fracture sin post menopausal. - second line after oral bosphosphonates. lower BMD and clinical RFs.
  • Seconday prevention osteoporotic frcture sin postmeniopausal - seocnd line after oral biphosphonates
• Teriparatide - restrictedus eby cost for severe osteoporisis/ Esp if multipel vetebral fractures + very low BMD + failur eot repond to antiresorptives. NICE say women 55+/ alSO FOR pmo, men, giop (STEROIDS). Duraiton tx now extended to 24months. most rel for those pretreated with bosphosphonates. SUbstantial rises in bone density final 6m/
• Romosozumab -Anabolic agent = Monoclocnal anti-sclerostin, whcih inhibits bone formation. Inhibition of sclerostin, enhance sosteoblast function, improves boe mas + reduces fracture. 210mg s/c monthly for 12months. Retsriced license for use in scotland, not endorsed by NICE.

Question 5

Guidelines Osteoporosis management

Answer 5

Question 6

Emergign therapie sin osteoporisis

Answer 6

—

• —Abolaparatide – Parathyroid hormone related protein analogue
• —Odanacatib- Cathepsin K inhibitor- initial promising results, but discontinued due to small increase in strokes

Question 7

Alendronic acin in osteoporosis

Answer 7

• Biphosphonate
• Reduces risk of vert, non vert and hip fractures.

Question 8

Risedronate in osteoporosis

Answer 8

• Lower boen affinitya ndf less ptoent than alendronic acid
• May enable greater access to osteocytes
• Possibly explains simialr efficacy to more potent antiresorptives

Question 9

Ibandronate in osteoporosis

Answer 9

• Bisphosphonate
• Monthly 150mg oral
• IV eveyr 3months - no renal toxicity
• Second line oral bosphosphonate

Question 10

Denosumab (prolia)

Answer 10

• highly potent, use din osteoporosis
• human monoclonal A against RANK ligant

Question 11

Teriparatide indications

Answer 11

• Restricte duse by cost
• Severe osteoporosis
• WHen sever eosteoporosis, esp if multiple vertebral fractures and v low BMD + failure ot respond to antiresorptives
• WOmen for age 55
• Licences for PM0, Men and GIOP (steroids)
• Duraiton treatment now 24months.

Question 12

ROmosozumab

Answer 12

• ANabolic agent
• Monoclonal anti-sclerostin antibosy in osteoporosis
• Inhibition sclerostin, enhance sosteoblast function, improves bone mss and reduces fractures
• 210mg s/c monthly for 12months
• Retsricted lience for ise in scotland. npt endorsed by nice

Question 13

Abolaparatide

Answer 13

—Parathyroid hormone related protein analogue

In osteoporosis (emergign therapy)

Question 14

Odanacatib

Answer 14

Emergeing therapy in osteoporosis

Cathepsin K inhibitor- initial promising results, but discontinued due to small increase in strokes

Question 15

Bisphosphonates general MOA

Answer 15

• Reduce bone turnover
• Increase boen density - decrease remodellign space, increase seocndary mineralisation
• Preserves boen structure