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UNUSUAL OSTEOPOROSIS
Case 1
∗ 73 year old man presented with recent onset
of back pain and weight loss.
∗ X-rays showed multiple vertebral fractures.
∗ PMH AF controlled with amiodarone.
∗ Non smoker, little alcohol.
∗ Differential diagnosis?
Case 1
∗ FBP
∗ Admission profile, bone profile, PSA
∗ ESR / CRP
∗ PPE, Bence Jones
∗ Testosterone
∗ TFTs, 24hr urinary cortisol
∗ Coeliac screen
Case 1 Investigations
∗ T4 96.9 pmol/L
∗ TSH < 0.02 mu/L
∗ Hyperthyroidism secondary to
amiodarone
Case 1 Diagnosis
∗ Increased frequency of bone remodelling
∗ Shortened cycle with bone formation
shortened more than resorption
∗ Leads to loss of bone with each cycle
∗ relative increased Ca -- decreased PTH--
decreased 1-25 Vit D -- decreased Ca
absorption and increased Ca excretion
Hyperthroidism and Bone
∗ Increased fracture rate
X 3 to 4 increased rate & only in part related
through BMD.
Hyperthyroidism and Fracture
∗ BMD increases on average 4% in first year.
∗ BMD returns to normal range within 3-5 yrs.
∗ But there remains an increased fracture rate
for up to 5 years.
∗ Therefore in severe osteoporosis use
antiresorptive therapy for 3-5 years.
Correction of Hyperthyroidism
Bone response
Case 2
∗ 51 year old man # elbow after fall off bicycle,
March 2017
∗ Keen club cyclist
∗ Previous #s in falls off bike
∗ Hip 2007
∗ Pubic ramus 2013
Case 2
∗ FBP
∗ Admission profile, bone profile, PSA
∗ ESR / CRP
∗ PPE, Bence Jones
∗ Testosterone
∗ TFTs, 24hr urinary cortisol and calcium
∗ Coeliac screen
∗ All normal
Case 2 Investigations
∗ Sherk et al. (2014)14 cycling (F)>1 year of competition history26–41Longitudinal (1 year) BMD of the hip decreases 1–2% after a
year of training and competition.
∗ Gómez-Bruton et al. (2013) 20 cycling19 control (M)10 h/wk16.4
Cross-sectional Lower BMD of young cyclists in some places.
∗ Guillaume et al.(2012)29 cycling (M)25,000–30,000 km/year26–5 Descriptive ND between groups on calcium and vitamin D
intake
∗ Nichols et al.(2011)19 cycling
18 control (M)11.1 h/wk
4.5 h/wk50–57Longitudinal (7 years) Cycling has not demonstrated positive effects on BMD. High rate of
osteopenia/osteoporosis in cyclists (84.2% and 89.5% after seven years)
∗ Abe et al.(2014) 14 cycling (masters)13 moderately active youngsters (M)17 years of training 20–71 Cross-sectional BMD lower
in femoral neck of cyclists versus control. ND in BMD of lumbar spine.
∗ Olmedillas et al. (2011)21 cycling
23 control (M)10 h/wk 4 h/wk15–21 Cross-sectional Lower BMD of the hip, leg and pelvis of cyclists versus control
∗ Campion et al. (2010)30 cycling
30 control (M)22–25 h/wk
<1 h/wk29 ± 3 28 ± 4 Cross-sectional Professional cycling affected negatively BMD (femoral neck: −18%)
∗ Penteado et al.(2010)31 cycling
28 control 21 h/wk20–30 Cross-sectional ND in BMD versus control
∗ Barry et al.(2008)14 cycling (M)>450 h/y27–44 Two groups: low and high doses of calcium supplementation during one year
Both groups decreased BMD of the hip and sub-regions, regardless of calcium intake
∗ Rector et al.(2008) 27 cycling 18 marathon (M)≥6 h/wk≥6 h/wk20–59 Cross-sectional 63% of cyclists had lumbar spine
osteopenia and were 7-fold times more likely to have osteopenia
Cycling and BMD
∗ Is low BMD in cyclists associated with higher
fracture rate?
∗ Why low BMD?
∗ Effect of Skeletal loading on osteocyte
∗ Lazy Bones may be right !
∗ Advise weight bearing exercise
Cycling and Fracture
Case 3
∗ 68 year old man presented with tiredness
after small CVA.
∗ PMH of AF.
∗ Lower thoracic back pain
Case 3
∗ FBP
∗ Admission profile, bone profile, PSA
∗ ESR / CRP
∗ PPE, Bence Jones
∗ Testosterone
∗ TFTs, 24hr urinary cortisol and calcium
∗ Coeliac screen
∗ Testosterone 2.8 (6.7-25.7)
Case 3 Investigations
∗ Very aware of postmenopausal bone loss. but
hypogonadism in men?
∗ Studies suggest up to 50% of osteoporosis in men is
secondary.
∗ Alcohol probably accounts for half of this and
hypogonadism ? a quarter.
Hypogonadism and Osteoporosis
∗ Testosterone(T) has direct effect on bone cells
through androgen receptor.
∗ T has indirect effect through peripheral
conversion of T to oestrogen via aromatase in fat
tissue.
∗ Stronger correlation between oestrogen and
BMD and fractures than T in men.
∗ Low T could be linked to increased fracture rate
through reduced muscle strength and falls
Testosterone and bone
∗ Treat hypogonadism in men when it is
symptomatic.
∗ Treat osteoporosis with bisphosphonates
(Denosumab) as per guidelines.
∗ Treat osteoporosis with testosterone
replacement when there is no alternative
therapy available.
Treatment
∗ Aromatase inhibitors
∗ Treat when T score is less than -2.0
∗ Androgen deprivation therapy
∗ Treat with bisphosphonates ( oral, iv)
∗ Denosumab licensed USA
Iatrogenic
Case 4
∗ 45 year old man presented with acute mid
thoracic back pain.
∗ Keen runner up to marathon level.
∗ Fatigue recently, not running and weight gain.
∗ No past medical history.
∗ X-rays showed 3 thoracic vertebral fractures
Case 4
∗ FBP
∗ Admission profile, bone profile, PSA
∗ ESR / CRP
∗ PPE, Bence Jones
∗ Testosterone
∗ TFTs, 24hr urinary cortisol and calcium
∗ Coeliac screen
∗ Urine Cortisol 4020 (<210) and subsequent CT
showed adrenal carcinoma
Case 4 Investigations
∗ Endogenous is very rare compared with
exogenous corticosteroids.
∗ Complex effect on bone metabolism.
∗ Direct bone cell effects with initial rapid
increase in bone resorption followed by long
term decrease in bone formation.
∗ Indirect effects through Vit D and calcium,
growth hormones, IGF and hypogonadism.
Glucocorticoid Induced Osteoporosis
(GIO)
∗ Standard relationship between BMD and
fracture risk does not apply.
∗ In GIO apply higher threshold for treatment
( T score -1.5).
∗ Bone microstructure is important.
∗ Trabecular bone is affected most.
∗ Vertebral fractures are often asymptomatic.
GIO and Fracture
∗ Lifestyle, weight bearing exercise.
∗ Calcium (1000mg) and Vit D (800iu).
∗ Depending on fracture risk
∗ Bisphosphonates oral (IV)
∗ Denosumab if C/I to bisphosphonates.
∗ New ACR guidelines
∗ Pred dose 2.5mg for > 3 months or 5 gm total
∗ Based on fracture risk and age < or > 40yrs.
Management of GIO

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Unusual Osteoporosis

  • 3. ∗ 73 year old man presented with recent onset of back pain and weight loss. ∗ X-rays showed multiple vertebral fractures. ∗ PMH AF controlled with amiodarone. ∗ Non smoker, little alcohol. ∗ Differential diagnosis? Case 1
  • 4. ∗ FBP ∗ Admission profile, bone profile, PSA ∗ ESR / CRP ∗ PPE, Bence Jones ∗ Testosterone ∗ TFTs, 24hr urinary cortisol ∗ Coeliac screen Case 1 Investigations
  • 5.
  • 6.
  • 7.
  • 8.
  • 9. ∗ T4 96.9 pmol/L ∗ TSH < 0.02 mu/L ∗ Hyperthyroidism secondary to amiodarone Case 1 Diagnosis
  • 10. ∗ Increased frequency of bone remodelling ∗ Shortened cycle with bone formation shortened more than resorption ∗ Leads to loss of bone with each cycle ∗ relative increased Ca -- decreased PTH-- decreased 1-25 Vit D -- decreased Ca absorption and increased Ca excretion Hyperthroidism and Bone
  • 11. ∗ Increased fracture rate X 3 to 4 increased rate & only in part related through BMD. Hyperthyroidism and Fracture
  • 12. ∗ BMD increases on average 4% in first year. ∗ BMD returns to normal range within 3-5 yrs. ∗ But there remains an increased fracture rate for up to 5 years. ∗ Therefore in severe osteoporosis use antiresorptive therapy for 3-5 years. Correction of Hyperthyroidism Bone response
  • 13.
  • 14.
  • 16. ∗ 51 year old man # elbow after fall off bicycle, March 2017 ∗ Keen club cyclist ∗ Previous #s in falls off bike ∗ Hip 2007 ∗ Pubic ramus 2013 Case 2
  • 17.
  • 18.
  • 19. ∗ FBP ∗ Admission profile, bone profile, PSA ∗ ESR / CRP ∗ PPE, Bence Jones ∗ Testosterone ∗ TFTs, 24hr urinary cortisol and calcium ∗ Coeliac screen ∗ All normal Case 2 Investigations
  • 20.
  • 21. ∗ Sherk et al. (2014)14 cycling (F)>1 year of competition history26–41Longitudinal (1 year) BMD of the hip decreases 1–2% after a year of training and competition. ∗ Gómez-Bruton et al. (2013) 20 cycling19 control (M)10 h/wk16.4 Cross-sectional Lower BMD of young cyclists in some places. ∗ Guillaume et al.(2012)29 cycling (M)25,000–30,000 km/year26–5 Descriptive ND between groups on calcium and vitamin D intake ∗ Nichols et al.(2011)19 cycling 18 control (M)11.1 h/wk 4.5 h/wk50–57Longitudinal (7 years) Cycling has not demonstrated positive effects on BMD. High rate of osteopenia/osteoporosis in cyclists (84.2% and 89.5% after seven years) ∗ Abe et al.(2014) 14 cycling (masters)13 moderately active youngsters (M)17 years of training 20–71 Cross-sectional BMD lower in femoral neck of cyclists versus control. ND in BMD of lumbar spine. ∗ Olmedillas et al. (2011)21 cycling 23 control (M)10 h/wk 4 h/wk15–21 Cross-sectional Lower BMD of the hip, leg and pelvis of cyclists versus control ∗ Campion et al. (2010)30 cycling 30 control (M)22–25 h/wk <1 h/wk29 ± 3 28 ± 4 Cross-sectional Professional cycling affected negatively BMD (femoral neck: −18%) ∗ Penteado et al.(2010)31 cycling 28 control 21 h/wk20–30 Cross-sectional ND in BMD versus control ∗ Barry et al.(2008)14 cycling (M)>450 h/y27–44 Two groups: low and high doses of calcium supplementation during one year Both groups decreased BMD of the hip and sub-regions, regardless of calcium intake ∗ Rector et al.(2008) 27 cycling 18 marathon (M)≥6 h/wk≥6 h/wk20–59 Cross-sectional 63% of cyclists had lumbar spine osteopenia and were 7-fold times more likely to have osteopenia Cycling and BMD
  • 22. ∗ Is low BMD in cyclists associated with higher fracture rate? ∗ Why low BMD? ∗ Effect of Skeletal loading on osteocyte ∗ Lazy Bones may be right ! ∗ Advise weight bearing exercise Cycling and Fracture
  • 24. ∗ 68 year old man presented with tiredness after small CVA. ∗ PMH of AF. ∗ Lower thoracic back pain Case 3
  • 25.
  • 26.
  • 27.
  • 28. ∗ FBP ∗ Admission profile, bone profile, PSA ∗ ESR / CRP ∗ PPE, Bence Jones ∗ Testosterone ∗ TFTs, 24hr urinary cortisol and calcium ∗ Coeliac screen ∗ Testosterone 2.8 (6.7-25.7) Case 3 Investigations
  • 29. ∗ Very aware of postmenopausal bone loss. but hypogonadism in men? ∗ Studies suggest up to 50% of osteoporosis in men is secondary. ∗ Alcohol probably accounts for half of this and hypogonadism ? a quarter. Hypogonadism and Osteoporosis
  • 30. ∗ Testosterone(T) has direct effect on bone cells through androgen receptor. ∗ T has indirect effect through peripheral conversion of T to oestrogen via aromatase in fat tissue. ∗ Stronger correlation between oestrogen and BMD and fractures than T in men. ∗ Low T could be linked to increased fracture rate through reduced muscle strength and falls Testosterone and bone
  • 31. ∗ Treat hypogonadism in men when it is symptomatic. ∗ Treat osteoporosis with bisphosphonates (Denosumab) as per guidelines. ∗ Treat osteoporosis with testosterone replacement when there is no alternative therapy available. Treatment
  • 32. ∗ Aromatase inhibitors ∗ Treat when T score is less than -2.0 ∗ Androgen deprivation therapy ∗ Treat with bisphosphonates ( oral, iv) ∗ Denosumab licensed USA Iatrogenic
  • 34. ∗ 45 year old man presented with acute mid thoracic back pain. ∗ Keen runner up to marathon level. ∗ Fatigue recently, not running and weight gain. ∗ No past medical history. ∗ X-rays showed 3 thoracic vertebral fractures Case 4
  • 35. ∗ FBP ∗ Admission profile, bone profile, PSA ∗ ESR / CRP ∗ PPE, Bence Jones ∗ Testosterone ∗ TFTs, 24hr urinary cortisol and calcium ∗ Coeliac screen ∗ Urine Cortisol 4020 (<210) and subsequent CT showed adrenal carcinoma Case 4 Investigations
  • 36.
  • 37.
  • 38.
  • 39.
  • 40. ∗ Endogenous is very rare compared with exogenous corticosteroids. ∗ Complex effect on bone metabolism. ∗ Direct bone cell effects with initial rapid increase in bone resorption followed by long term decrease in bone formation. ∗ Indirect effects through Vit D and calcium, growth hormones, IGF and hypogonadism. Glucocorticoid Induced Osteoporosis (GIO)
  • 41. ∗ Standard relationship between BMD and fracture risk does not apply. ∗ In GIO apply higher threshold for treatment ( T score -1.5). ∗ Bone microstructure is important. ∗ Trabecular bone is affected most. ∗ Vertebral fractures are often asymptomatic. GIO and Fracture
  • 42. ∗ Lifestyle, weight bearing exercise. ∗ Calcium (1000mg) and Vit D (800iu). ∗ Depending on fracture risk ∗ Bisphosphonates oral (IV) ∗ Denosumab if C/I to bisphosphonates. ∗ New ACR guidelines ∗ Pred dose 2.5mg for > 3 months or 5 gm total ∗ Based on fracture risk and age < or > 40yrs. Management of GIO