Metabolic disorders Z. Rozkydal Metabolic disorders- osteopathy •Osteoporosis •Osteomalatia •Primary hyperparathyreoidisms •Secondary hyperparathyreoidisms: • - renal osteodystrophy • - gastrointestinal osteodystrophy • •Composition of bone •50 % anorganic material (hydroxyapatit crystals) • •25 % organic bone matrix (osteoid): • 90 % collagen type I • 10 % other proteins (osteocalcin, • osteonectin, proteoglycans, enzymes) • •25 % water binding on collagen and proteoglycans •Skeleton •Weight 5 kg •Cortical bone 4 kg •Trabecular bone 1 kg Kostra Kosti •Cortical bone Trabecular bone Osteo- haverský systém •Cortical bone- Haversian system Osteo- haverský systém2 Osteo- spongioza1 Osteo- spongioza2 •Trabecular bone BP - kost kortikální a trabekulární jpg •Trabecular bone: •- 20% of the skeleton •- 80% of remodelling • • •Cortical bone: •- 80% of the skeleton •- 20% of remodelling •Collagen type I. •Osteoblasts: •They produce osteoid- organic part of matrix •They provide mineralisation of bone •They produce alcaline phosphatase •– indicator of the synthesis of proteins • Remodelace kosti schéma •Osteoclasts: •Large multinuclear cells •They are localised in Howship lacunes on the •surface od bone •They produce acid phosphatase and lytic enzymes •They dissolve hydroxyapatite crystals and bone matrix Remodelace kosti schéma •Osteocytes •They lie in lacunes of corticals and trabecular bone •They are connected wit canaliculi •They maintain metabolism of bone • Remodelace kosti schéma BP- bone remodeling •Remodelling of bone •Resorption is finished in 2 weeks •Mineralisation up to six months Osteoporosis is a systemic disorder of the skeleton •Diminished strength of bone •Low bone density •Impaired microarchitecture •Tendency to fractures •Loss of organic and anorganic bone Osteoporotická kost BP- graf BMD •Peak bone mass - in 25-30 years of age Bone loss • •Before menopause 0,3 % / year • •After menopause 3 % / year Osteoporosis •primary: • idiopathic • postmenopausal - type I. • involutional (senile) - type II. •secondary - type III. Clinical symptoms •Back ache •Diminished ability to work •Problems with walking • and standing •Problems with lifting heavy objects •Sharp pain- in a case of fracture Eliška- OP 1 Examination •Tenderness on spinous process •Limited movements of the spine •Paravertebral spasm •Thoracis kyphosis •Widow´s hump •Lower lenghth of the stature Vdovský hrb klin Fosa-skelet Imaging techniques •X- ray shows bone loss of 30 % or more • •DEXA • •QCT • •Ultrasonography Vdovský hrb rtg • •DEXA – Dual Energy Absorptiometry •BMD in g/cm2 •T score •Z score •Change Eliška OP 2 Eliška OP 3 •L1-L4 •Hip Total • •Hip neck Eliška OP 4 Fosa-dexa Postmenopausal osteoporosis •80% of all cases •25 % of female are involved •Between 50- 65 years •Loss of estrogens- high activity of osteoclasts •Trabecular bone most often affected Fosa-kyfóza •Over 70 years, ratio female: male = 2 : 1 •The cause: no production of osteoblasts in bone marrow •Cortical and trabecular bone •Senile osteoporosis • Secondary osteoporosis •Corticosteroids •Hyperthyreosis •Malabsorption •Alcoholisms •After trnsplantations Osteoporosis in men • •Primary • •Hypogonadism • Risk factors •Low stature •White and yellow ethnics •Low physical activity •Low nutrition with calcium Risk factors •Higher age •Low BMI •Occurence in family • Hypogonadal conditions •premature amenorhoea •surgery of ovaria •oligomenorhoea, amenorhoea •nullipara •low endogen estrogen •mental anorexia Risk factors- drugs • •corticosteroids •anticonvulsives •diuretics •heparin Risk factors •malabsorption •chronic disorders of liver •chronic disorders of kidney •alcohol Prevention of osteoporosis •Maximal peak bone mass •Management of disorders in children •Removal of risk factors •Management of gastrointestinal disorders •Nutrition with calcium and vitamin D •Physical activity •Management •Analgetics •Physiotherapy •Nutrition (proteins, calcium) •Calcium - 1300 mg/day •Vitamin D - 800 I.U/day •Drugs •Orthesis •Surgery Fosa-cvičení •Nutrition •BMI 23-25 • •Proteins 1,0 g/kg/day • •+ 30g of proteins /day • •IGF-1 – insulin like growth factor • • • •Calcium •1,5 g / day • •Application in the evening • Calcium •Calcium eff. Pharmavit 500, 1000 mg •Calcium Sandoz forte 500 mg eff. •Calcium Slovakofarma eff. •Maxi-Kalz eff tbl, 100, 500 mg. •Vitacalcin pulvis, tablety •Biomin H plv.- Ca, Mg + IGF-1. OP KombiKalz Calcium •Kombi-Kalz pulv, 1000Ca+ • 880 IU vit D. •Osteocare tbl. •Caltrate plus tbl •Calcium 500 + vit D3 eff. •Calcium D forte cps •Calcicew OP KombiKalz •7-dihydrocholesterol •In the skinn -UV beams -cholekalciferol •In liver conversion to 25-OH vit. D3 •In kidneys conversion to 1,25 dihydroxy-vit. D3 •Active agent is kalcitriol 1,25 (OH) D3. • •80-90% of daily use is covered by sun radiation • •Vitamin D •Vitamin D •60 % off seniors have hypovitamonosis of •vitamin D •Optimal level in blood is 80 nmol/l •Hypovitaminosis - bellow 20 nmo/l • •Dosage: 800 IU/day • • • Vitamin D •Infadin gtt, vit D cps., Vigantol oel, gtt •Rocaltrol cps, Vitamín D Slovakofarma cps •Calciferol inj. •1 alfa (OH) D3 – alfakalcidol - Alpha D3 •1 alfa (OH) D2 – doxercalciferol ( Hectorol) •22 oxakalcitriol (OCT) •19 nor 1,25 (OH)2 D2 – parikalcitriol (Zemplar) • Inhibition of bone resorption • •Bisphosphonates •SERM •Stroncium ranelate •Calcium • Fosa-páteř Stimulation of bone formation • •Vitamin D •Anabolics •Teriparatid •Stroncium ranelate • Fosa-páteř •HRT •no evidence of effect OP Livial Bisphosphonates •Incorporation in HA crystals and matrix • •Inhibition of formation, agregation and dissolution of crystals • •Inhibition of bone resorption OP- Fosamax •Fosamax Bisphosphonates •Reduction of activity of osteoclasts •Induction of apoptosis of osteoclasts •Bisphosphonates - indications •Osteoporotic fractures • •All forms of osteoporosis • •Paget ´s disease of bone • •Hypercalcemia in carcinomas od myeloma • • •Pamidronate - Aredia inj. • •Clodronate – Bonefos inj, cps., Lodronat inj, cps. • •Ibandronate – Bonviva tbl., Bondronate inj. • •Alendronate – Fosamax 70 mg tbl., Alendros tbl. • •Risedronate - Actonel tbl. • •Zoledronate – Aclasta inj. •Bisphopsphonates SERM - selective modulators of estrogen receptors •Raloxifen (Evista) •Agonists on bone and cardiovascular apparatus •Antagonists on endometrium and breast •They bind on the same place as estrogenes • (receptors alfa, beta ) •Strontium ranelate •Dual affect- •Reduces bone resorption •Increases bone formation • •Prevents loss of trabecular bone and stimulates its apposition • •Increases mineralisation of bone OP- protelos •Teriparatid – synthetic parathormon 1- 34 fragment •Stimulates bone formation •Stimulates osteoblasts •and remodelation •Improves the strength •of trabecular and cortical •bone • OP Forsteo • •Osteoporosis with corticosteroids •Condition after transplantations •Cushing syndrom •Hyperthyreosis •Rheumatoid arthritis •Osteogenesis imperfecta •Fibrous osseous dysplasia •Osteomyelitis •Myeloma, tumors, osteolytic metastasis •Malnutrition •Algoneurodystrophy • • •Differential diagnosis Osteomalatia •Systemic disordes in adults •Bone is in a form of nonmineralised osteoid •Calcium is not layed in HA crystalls •Bone is soft •The cause: lack of vitamin D OM4 OM5 •Osteomalatia RO5 •Osteomalatia Symptoms •Diffuse pain in skeleton •Muscle weakness •Tendermess of bones •Deformities of bones •Thoracic kyphosis Laboratory tests •High level of alcaline phosphatase •High level of bone isoenzyme of ALP •Low level of calcium •Normal level of phophorus •Radiological finding • •Rarefaction of skeleton •Narrow cortical bone •Looser´s zone of remodelling - non mineralised osteoid - •Biconcave shape of vertebras •coxa vara •Protrusion of acetabulum •Thoracic hyperkyphosis Nik_0030 Nik_0011 Nik_0016 •Osteomalatia Prevention •Vitamin D - sun radiation and in food •Application of vitamin D in renal and liver disorders Therapy •Vit. D 10 000 IU per day i.m. •Calciferol inj. •Vit. D p.os 2000 IU daily •Calcium 1000 - 2000 IU daily •Food with milk, sea fish •Rickets •1. Lack of vitamin D •2. Lack of phosphates •Inability to calcify of matrix •Bone is soft •Bending of bone •Wide growth plates •Metaphysis is wide •Deformities of bones • OM3 OM1 •Rickets •Fatigue •Entlargement of abdomen •Walking ability - worsened •Craniotabes •Large fontanels •Dentic diturbences •Caput quadratum •Harrison´s groove •Rachitic rosary •Pectus carinatum •Crura et coxa vara •Pedes plani OM1 •Management •Vitamin D 500- 1000 IU/day 10 weeks •Sun radiation •Milk products with vitamin D • •Orthesis •Osteotomies Hyperparathyreoidisms - HPT • •Adenoma of parathyroid glands •Hyperplasia of parathyryoid glands •Carcinoma of parathyrdoid glands Primary HPT •Nefrolithiasis, polyuria, polydypsia •Osteodystrofia fibrosa cystica generalisata •Gastrointestical problems •Acute pancreatitis, cholelithiasis •Muscle weakness, fatique, bone pain •Chondrocalcosis, calcifications HPT 1 HPT 2 Primary HPT •High level of calcium •Hypofosfatemia •Hyperfosfaturia •High level of ALP •High level of parathormon HPT 2 •Radiological finding • •Rarefaction in skeleton •Narrow corticalis bone •Resorption in phalangs •Large cysts as bone tumors • •Kyphosis •Coxa vara •Fisures and complete fractures • HPT 2 HPT 3 HPT 3 Nik_0002 Nik_0018 •Primary HPT RO1 RO2 •Renal osteodystrophy •- secondary HPT in renal disorders •Secondary hyperplasia of parathyroid glands • RO3 •Renal osteodystrophy • •Fatigue, bone pain •Muscle weakness •Fractures • •Th: Treatment of renal disorders • vitamin D3 • calcium • • • •Resection of the stomach or intestine, •gall bladder problems, coeliakia, •pancreatitis • •Pain in bones •Muscle wekness •Pseudofractures •Deformities of bone •Secondary HPT •- Malabsorption of vitamin D Nik_0026 Nik_0027 Nik_0010 •Secondary HPT •- malabsorption of vitamin D Paget ´s disease of bone •Sir James Paget in 1876 •Chronic disease •Slow viral infection (distemper virus from • group of paramyxovirures) •GB, USA, Australia, New Zeland, France Germany, Malta. Morbus Paget •1. Osteolytic phase •2. Mixed phase •3. Osteoblastic phase Morbus Paget •Monoostotic form - 20 % •Polyostotic form • •95 % are asymptomatic •5% symptomatic Symptoms •Pain •Fatique •Deformities •Complications Nik_0014 Nik_0016 Clinical symptoms •Mild •Modrate •Severe Nik_0011 Nik_0017 • Nik_0015 Nik_0020 Nik_0023 Nik_0023 Nik_0024 Nik_0010 Nik_0014 Nik_0013 Nik_0010 Nik_0015 Nik_0016 Nik_0002 Nik_0021 Nik_0019 Nik_0001 Nik_0004 • •Gothic arch Nik_0005 Nik_0006 Nik_0028 Nik_0026 •Complications • •Fissures •Fractures •Osteoarthrosis •Deafness •Neuralgia n. trigeminus •Basilar invagination •Vertebrobasilar insuficiency •Paraparesis, sciatica •Dental problems Nik_0028 •Hypertension •Ischemic heart disease •Cardiomegaly • •Neoplasmatic degeneration •sarcoma •Nefrolithiasis •Calcifications •Complications Management •Bisphosphonates (Fosamax 40 mg daily • three months, Pamidronate, Zoledronate •Calcitonin nasal spray, s.c. •Calcium •Therapy of complications •Osteosynthesis of fx •Total knee and hip replacement Nik_0011 •Charnley total hip arthroplasty