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See also: VitaminD |



  • NOGG guidelines:
  • NOGG Executive summary:
  • NOGG Pocket Guide:
  • Diagnosis:
    • Osteoporosis = BMD via DXA at femoral neck >=2.5 SD below young adult female (T<=-2.5)
  • Investigations: Hx, Exam, Ix to
    • Aim
      • exclude mimics: osteomalacia, myeloma
      • identify cause and contributory factors
      • assess risk of subsequent fractures
      • select most appropriate form of Tx
    • Routine
      • Hx & Exam
      • FBC, ESR/CRP, Ca, Alb, Crea, PO4, AP, ALT/AST
      • TFT
      • Bone densitometry (DXA)
    • Other procedures, if indicated
      • Lateral radiographs of LS/TS or DXA-based vertebral imaging
      • Protein immunoelectrophoresis and urinary BJP
      • Testo, FSH, LH (in men)
      • Prolactin
      • 24h-urinary cortisol/DST
      • Endomyseal/Tissue transglutaminase antibodies
      • Isotope bone scan
      • Markers of bone turnover, when available
      • Urinary calcium excretion
  • Clinical RF used for the assessment of fracture probability
    • Age
    • Sex
    • BMI<=19kg/m2
    • Previous fragility fracture, particularly of the hip, wrist and spine incl morphometric vertebral fracture
    • Parental Hx of hip fracture
    • Current glucocorticoid treatment (any dose, by mouth for three months or more)
    • Current smoking
    • Alcohol intake of >=3units/day
    • Secondary causes of osteoporosis, including
      • RA
      • Untreated hypogonadism
      • Prolonged immobility
      • Organ transplantation
      • T1DM
      • Hyperthyroidism
      • GI disease
      • CLD
      • COPD
    • Falls [not currently in FRAX]
  • Case finding
    • Women with prior fragility fracture: consider treatment (w/o further risk assessment, except younger)
    • In presence of other clin RFs: determine 10y probability of major osteoporotic fracture (FRAX)
    • In patients requiring BMD measurement, fracture probability should be recalculated
    • Intervention thresholds [aj] 10% major osteoporotic fracture risk vs age
      • 40y>5%; 50y>7%, 60y>12%, 70y>80%, 80y>28%
  • Treatment
    • General management
      • assessment of risk of falls and prevention
      • maintenance of mobility
      • correction of nutritional deficiencies, esp Ca>1000mg/d, VitD>=800 IU/d, Protein>1g/kg body weight/d
    • Pharmacological interventions (effective for V=vertebral / H=hip fractures, also licensed for M=Men, G=Glucocorticoid-induced osteoporosis)
      • Bisphosphonates
        • esp generic Alendronate (VHMG)
        • Ibandronate (V)
        • Risedronate (VH)
        • Zoledronate (VH)
      • Raloxifene (V,H)
      • Strontium ranelate (VH)
      • Teriparatide (VM)
      • PTH (1-84) (V)
      • Other approved interventions: Calcitonin, Calcitriol, Etidronate, HRT

Teaching Diab/Endo 22-Oct-2009

Osteoporosis Guidelines

Caroline Jagger, Osteoporosis Specialist Nurse, MRI

  • severe osteoporosis = T<-2.5 & associated fractures
  • primary osteoporosis = senile = postmenopausal
  • NICE guidelines: only postmenopausal women
    • 1st choice: Alendronate weekly (cheap, but GI SE - check after 4 weeks)
  • NOGG (National Osteoporosis Guideline Group): guidance for men & women, use of FRAX tool (predicts 10y fracture risk)
  • eg: 75y women with fracture: may treat without DEXA
  • DEXA T=-2.5 may equate T=-3.5 on qCT
  • Strontium: ?; a/w DVT, DRESS
  • Zolendronic acid: 5mg annual infusion as iv alternative (SE: flu-like sy for 3d, occas. bone pain for 6wks, rarely AF, very rarely osteonecrosis of jaw [1:100k at standard doses, 1:1k in oncology eg 4mg q1mth]
  • BMD: 80% genetic + 20% environmental
  • NB: lumbar BMD may icr with age due to degenerative disease

Vitamin D and metabolic bone disease

Dr Michael Davis, MRI
  • colecalciferol=VitD3=sunshine; synthesis affected by
    • sunlight angle: shadow should be less than height (in temperate climates: only sufficient during May-Sept)
    • skin phototype (see Fitzpatrick'75): minimal erythemal dose: x2 causes sunburn, x0.5 enough for VitD synthesis
    • icrd age: dcrd skin thickness: dcrd VitD synthesis
  • UVB 290-320: responsible for VitD synthesis in skin
  • almost all diets are insufficient in VitD to comply with current recommendations of optimal VitD levels: therefore either supplementation or sunshine
  • D2=Ergocalciferol: food/supplements, D3=Colecalciferol: additives/sunshine?#, 1,25OHD=Calcitriol
  • 25OHD=storage form of VitD=measured in assays
  • hypercalcaemia: dcrs 1-hydroxylation
  • 1,25OHD: icrs intestinal Ca absorption
  • PTH: on bone; on kidneys: icrs 1-hydroxylation: icrs gut Ca absorption
  • Metabolic bone disease
    • Osteomalacia/Rickets: soft bendy bones, painful, proximal muscle weakness if due to dcrd VitD
    • Osteoporosis: asymptomatic until fracture
    • Paget's disease
  • Bone remodelling units: 4 stage cycle (80% of bone formed during 9mth cycle length)
    • Osteoclast activity: bone resorption
    • Osteoblast precursor activity: putting down [mainly T1] collagen (Osteoid)
    • Osteoblast activity: bone formation (if problems with this step: osteomalacia)
    • Resting phase
  • 1780s: cod liver oil for 'rheumatism' at MRI (Percival); Rickets: English disease; 1822: sunshine cures Rickets; 1932: VitD isolated
  • Development of VitD deficiency from VitD insufficiency:
    • VitD insuff: dcrd Ca: icrd PTH: icrd conversion of 25OHD to 1,25OHD: icrd gut Ca reabsorption: restored Ca levels at expense of icrd PTH: ultimately leads to 25OHD depletion: =VitD deficiency
  • Current Recommended Daily Dose: 10mcg (400iu) VitD where diet is the only source: only to prevent severe VDD, i.e. osteomalacia/rickets
  • VDD: associations
    • malabsorption, chron liver dis, gastric bypass, PHPT, AED, etidronate, vegetarian (NB: meat protects ?how), immigrants (clothing, eg Hindus: veget+clothing)
    • renal, hypophosphataemia (XLH, acquired tumoral), Cadmium
  • Ix: Corr Ca [lo / lo-nl], PO4 [lo / lo-nl], AP, Crea [nl], PTH [hi], +-VitD
    • NB: occas'ly: pseudohypoparathyroidism of VDD: vlo Ca, hi PO4, (hi) PTH - eg in young adults
    • Xrays: occasly Looser zones
  • Rx Osteomalacia: (long-term treatment)
    • 800iu od; or
    • 50k iu od for 5-10d; or
    • 300k iu IM q 1-3mth (if malabsorption)
  • Rx VDD
    • 800iu VD od; or
    • 40k D3 / 50k D2 mthly [CAUTION: NOT DAILY!! else TOXIC]; or
    • 300k iu VD 3mthly: check Ca q3-4mth
  • Rx with Calcitriol: only if VDDR or renal dis; need to be assessed q3mth
  • VDD: icrd PTH: exacerbates osteoporosis (esp cortical bone, eg DEXA forearm)
  • 25OHD:
    • <5ng/mL: hi risk of osteomalacia (esp if lo meat diet)
    • <10ng/mL: moderate risk of osteomalacia
    • <20ng/mL: moderate risk of icrd PTH drive
    • <30ng/mL: small risk of icrd PTH drive
  • Prevention: exercise, casual sunshine 20-30min/d
  • Symptoms of osteomalcia: hip pain, waddling gait, proximal myopathy, Looser's zones: sy usu only if VD<5ng/mL
  • always check for coeliac (eg W Ireland)

Bone markers in osteoporosis

Prof Bill Fraser, Liverpool University
  • Markers of bone resorption
    • [Type 1] collagen crosslinks: PYD/DPD
    • Telopeptide NTX/CTX ***
    • crosslinked C-terminal telopeptide 1CTP
    • Acid phosphatase (TRAP5b)
    • [Hydroxyproline: NB: reutilised]
    • [Ca: NB: reutilised]
  • Markers of bone formation
    • Alkaline phosphatase (Bone-[specific]=B[S]AP) *
    • Osteocalcin: [NB: difficult in transport]
    • Pro-collagen peptide
    • P1CP/P1NP (Procollagen Type 1 N-propeptide#?) **
  • Preferred:
    • EDTA-Plasma-CTX [£12] and
    • P1NP [any sample]: esp. in Teriparatide therapy
  • Other tests available: FGF23
  • Clinical use of bone turnover markers
    • baseline: if very hi, consider alternative causes (Paget's, tu, HCM, toxicosis, osteopotegrin Ab, ...)
    • marker of compliance: bisphosphonate dcr markers by at least 50%;
    • may help with fracture risk prediction in future
  • Marker targets: aim lower quartile
  • BMD change after bisphosphonate treatment only accounts for 4-40% risk reduction, whereas:
  • Bone marker change accounts for 25-60% risk reduction
  • eg the greater the BAP dcr the greater hip fracture risk reduction
  • Alendronate absorption: 40% at 30min, 90%+ at 1hr (before ingestion of any food or tablets)
  • Clowes JCEM'04 on compliance and response to bisphosphonate therapy
  • "Non-response" to bisphosphonates: usu due to wrongly/not taking them
  • Teriparatide: PTH(1-34): BMD icr 2.6-13.7%, vertebr # dcr 65% (20mcg=licensed dose), 69% (40mcg)
    • NB: different effect on cortical vs trabecular bone; ? icrd wrist fractures
    • NB: tachyphylaxis if used in hypoparathyroidism [less if PTH(1-84) used]
  • transverse midshaft femoral fractures: ? relationship to bisphosphonates: causality uncertain (if used in correct patients)
  • Alendronate plus Ca-VitD better than Alendronate alone

Interventional radiology for osteoporosis

Dr Richard Whitehouse, MRI
  • vertebral fractures very underreported (both XRays and CT): ask for sagittal image reconstruction or review
  • vertebral fractures: {wedge | biconcave | crush}: usu if >25% depression
  • Swiss cheese analogy of errors and possible harm: only if happen to be aligned
  • vertebroplasty: injection of cement
  • kyphoplasty: = vertebroplasty with prior balloon inflation

Journal Club

  • Seleena Farook: Denosumab NEJM'09Aug: 60mg s.c. q6mth; NB: FDA ? icr in tumours (breast cancer subgroup)
  • Simeen Akhtar: Vertebroplasty NEJM'09Aug: no better than sham procedure / facet joint injection; NB: Charlson comorbidity index for 10y mort risk

Case presentation: Oncogenic osteomalacia

Claire Higham
  • oncogenic osteomalacia = hypophosphataemic osteomalacia
  • due to FGF23 (fibroblast growth factor 23)
  • acting via FGF-receptor (and affected by KLOTHO protein) in proximal tubule
  • FGF23 pathway: revealed molecular basis of AR-hypophosphataemia, XL-H, AD-H
Subpages (1): Osteoporosis