News in osteoporosis Rozkydal, Z. I. ortopedická klinika MU FN u sv. Anny v Brně •DXA • •FRAX • •Laboratory tests • •Imaging methods •1. Diagnostic tools •DXA – Dual Energy Absorptiometry •BMD v g/cm2 •T score •Z score •Change Eliška OP 2 Eliška OP 3 •L1-L4 •Hip Total • •Hip neck • •Wrist Eliška OP 4 •Strength of bone •Density from BMD predicts only •60-75 % od mechanical power of bone • •Quality of cortical and trabecular bone, •collagen and bone mineral • • •Cumulation of microdamage •and microfractures • •Remodelation of bone: •-permanent removal of old • and damaged bone • • OP 4 • • •Microcracks •FRAX •FRAX •– fracture risk assessment tool •10 year risk of a majer fracture • • • • Age Sex Weight Height Sustained fractures Fracture in parents Smoking Alkohol 3 or more units/day Corticosteroids Reumathoid artritis Secondary osteoporosis •Clinical data •Combination DXA + FRAX •Laboratory tests •Calcium •Phosphorus •ALP, bone isoemzyme of ALP •Vitamin D normal level: 20-80 ng/ml •Parathormon •Osteocalcin •CTX- C terminální peptid kolagenu •NTX- N terminální telopeptid kolagenu •Pyridinolin, deoxypyridinolin •Acid phosphatase • • •Normal calcium 2,0 – 2,75 mmol/l •Normal phosphorus 0,7- 1,5 mmol/l. • • •Bone formation • •ALP normal level 2,7 ukat/l in man and 2,3 ukat/l i woman. •- indicator of osteoblasts function. Marker of bone formation. •High levels in osteomalatia !! • •Bone isoenzyme ALP- marker of bone formation. • •Osteocalcin 3,4- 11,7 ng/ml u mužů, a 2,4- 10,0 ng/ml u žen. • •C terminal propeptid of collagen I (PICP) •N terminal propeptid of collagen I (PINP) - products of collagen synthesis • • • • • Bone resorption Tartrate resistent acid phosphatase – marker of bone resorption Pyridinolin and deoxypyridinolin (crosslinks) - marker of collagen degradation - CTx- (C terminal peptid of collagen I) NTx (N-terminal peptid of collagen I) - products of proteolytic resorption of collagen in bone - Vitamin D 40-80 ng/ml, under 20 ng/ml – advances hypovitaminosis Parathormon normal level 10-65 ng/ml. •HR- pQCT • •Pair biopsies- histology, histomorfometry • 2 D micro CT, microindentation • SEM • •Finite element analysis • •Raman microspectroscopy • • • • •Diagnostic tools •HR- pQCT • •High resolution, peripheral, •quantitative CT • •Noninvasive meassurement •of bone morphology • •Virtual biopsy • •Assess microarchitecture •up to 82 µm B Scanco 5 OP 6 •Xtreme CT •Assess thickness •of cortical bone • • B Scanco 1 •SCANCO •Xtreme CT •HR qCT B Scanco 3 Placebo 36 months PROTELOS 36 months •Pair biopsies- before and after treatment P zl •Histology •4 t. • • • • • • • • •8 t. •Kontrola OVX a SR B histomorfo 1 •Histomorfometry •Povrch kosti •Mineralizovaný povrch •Erodovaný povrch •Tloušťka trabekul •Konektivita trámců •Trabekulární objem •Kortikální tloušťka • B SEM2 •SEM: canaliculi between osteocytes •Healthy bone •FEA- finite element analysis • Trabecular bone (upto 82 µm) B Scanco 2 •Plates B Scanco 2 •Osteoporotic bone •Rods •Increases after 40 years of age - begins with resorption around Havers canal •Raman microspectroscopy •- cortical porosity B kortika 2 •Raman microspectroscopy •2. Frailty syndrom 1.Loss of weight 4-5 kg/year 2.Exhaustion 3.Muscle weakness / handgrip more than 20 % 4.Lower velocity of gait less than 20 % 5.Lower physical activity less than 20 % 6. 6. 6. • •Frailty syndrom •Subclinicaly •Early frail •Late frail •Endstage frailty syndrom: terminal geriatric deterioration •Frailty syndrom •Disposition to falls •Disposition to organ decompensation •Worsening of cognitive functions •Need for help in daily activities •Sarcopenia •Osteoporosis • •Low level of vitamin D • •Occurence • •Advanced age •7 % persons over 65 years •25 % persons over 75 years • •Loss of muscle power 20 % in 65-70 years •Loss of muscle power 60 % in 80 years • •Cause: longlasting deficiency of vitamin D •Risk factors of frailty syndrom •Cardiovascular disease •Diabetes mellitus •Atherosclerosis •Renal failure •Neurologic disorders •Obesity •Hormonal dysfunction •Hypovitaminosis D •Prevention and treatment of frailty syndrom •Frailty syndrom is reversible • •Nutrition and proteins 1,3 g/kg/day •Vit D 800 IU/day till 2000 IU/day •Vigantol 1 drop = 500 IU, alpha kalcidol 1 µg • •Strengthening of muscles, exercise, walking •Strengthtening of stability, prevention of falls •Prevention of atherosclerosis •Management of other comorbidities •Aleviating of pain •Stop walking when talking •3. Sarcopenia •Loss of muscle substance more than 20-30 % • •Dysbalance between synthesis and degradation of muscles •(myostatin, glucorticoids, sexual hormons, insulin, IGF-I ) • •Osteopenia • •Sedentary way of life •Sarcopenia •Muscle densitometry: below 2 SD – man under 7,26 kg/m2 • - woman under 5,45 kg/m2 •MRI • •Hand grip- dynamometr •Flexion- extension of the knee •Maximal forced breathing out •Velocity of gait •Test of balance •Get up and go test •Walking on stairs •Consequenses of sarcopenia •Lower physical activity (myosteatosis, sarkopenic obesity) • •Sarcoporosis • •Higher risk of falls • •Risk factors for developing of sarcopenia: •Parkinson sy, multiple sclerosis, CVA, catarracta • • •Medication •Vit D 800 IU/day till 2000 IU/day •Vigantol 1 drop= 500 IU •Alpha kalcidol 1 µg • •Testosteron •Ghrelin •GH secretogoga •Estrogens •Leptin • •4. Management •Farmacotherapy of osteoporosis •diminishes risk of fragility fractures •only 20-50 % • •+ frailty syndrom •+ sarcopenia •+ osteoarthrosis •+ other comorbidities •+ prevention of falls F koubová 1 •Medication Bisphosphonates: Alendronate (Fosavance) Risedronate (Actonel) Ibandronate (Bonviva) Zolendronate (Aclasta) Denosumab (Prolia) Stroncium ranelate (Protelos) Parathormon, teriparatid – (Forsteo) SERM- bazedoxifen Fosa-páteř Protection to prevent vertebral fractures • •Corresponding NNT •9 •21 •14 •20 •21 •16 •15 •Ringe JD, et al. Rheumat Int. 2010;30(7):863-869 •Cummings SR et al. N Eng J Med. 2009;361(8):756-765 •NNT: Number of patients Needed to be Treated •Absolute risk reduction for vertebral fracture (%) Slide mise sur e-media. •Reginster JY et al. Drugs 2011; 71(1):65-78 ARR= absolute risk reduction; NNT= number needed to treat (to prevent one event over 3 years); NS = not statistically significant; RRR= relative risk reduction. Comparison of antifracture efficacy Vertebral fracture •Absolute risk reduction •for hip fracture (%) •Corresponding NNT •2.1 •NA •0.3 •1.1 •1.1 •1.1 •NA •Ringe JD, et al. Rheumatol Int. 2010;30(7):863-869 •Cummings SR et al. N Eng J Med. 2009;361(8):756-765 •NNT: Number of patients needed to be treated •NA: no evidence available Protection to prevent hip fractures •334 •91 •91 •NA •NA •91 •48 Slide mise sur e-media. a Data over 5 years. ARR= absolute risk reduction; NNT= number needed to treat (to prevent one event over 3 years); NS = not statistically significant; RRR= relative risk reduction. •Reginster JY et al. Drugs 2011; 71(1):65-78 Comparison of antifracture efficacy Hip fracture •New agents Monoclonal sclerostin antibodies Romosozumab Blosozumab Osteoformative effect Sclerostin – inhibitor of osteoblasts production from osteocytes stimulates bone resorption via RANKL Inhibitors of katepsin K- inhibition of bone resorption Odanatocibe •Thank You for Your attention B- černá díra mléčné dráhy Black Hole of the Milky Way