Osteoporosis

Jana Čepová

ÚLCHKB

2.LF a FN v Motole, Praha

OsteoporosisIn Czech republic osteoporosis affects

12% inhabitants (1,2 mil.)

over 50 years:15% men, and 33% women

over 70 years:39% men, and 47% women

In next 20 years expected grow of 50 % !!

Osteoporosis

Osteoporosis is a disease characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk (WHO,1998).

Bone tissue

Outer part:

70% - substantia compacta (solid bone)…cortical bone

renewal 3% per year

Inner part :

20% - substantia spongiosa (spongy bone)…trabecular bone

renewal 25% per year

Bone function

- support and protection of various organs of the body

- production of red and white blood cells

- minerals storage (calcium, phosphorus, magnesium)

Composition of the bone

- 35% organic matrix:

(90% collagen, 5% osteocalcin, osteonectin, proteoglycans, sialoproteins, 2% osteoblasts, osteocytes, osteoclasts)

- 65% minerals:

(85% hydroxyapatite, calcium carbonate, calcium fluoride, magnesium phosphate, alkalic salts)

Types of osteoporosis

- postmenopausal

- GIOP

- men's

- child’s

- secondary (malabsorption, chronic steroid medication, multiple myeloma, celiac disease, immobility, multiple sclerosis…)

Secondary Osteoporosis

- hypogonadism, thyrotoxicosis, vit. D deficiency

- chron. steroid medication

- malabsorption, stp. gastrectomia, celiac disease…

- immobility, space travel

- multiple myeloma, lymphoma …

- medications –antiepileptics, heparin, MTX, cyklosp.A…

- osteogenesis imp.

- Rheumatoid arthritis, lupus erythematosus

Symptoms of osteoporosis

Osteoporosis itself has no symptoms

- Back pain

- decrease of body height of > 3 cm

- bone fractures at common activity or at minimal trauma

Osteoporosis?

Diagnose of osteoporosis• Medical history and clinical examination• osteodensitometry: DEXA, (UZ, QCT)• rtg examination of Th and L backbone, ev. of femur and of

radius• skeleton scintigraphic imaging• basic biochemical markers of osteoformation: osteocalcin,

bone iso-ALP • basic biochemical markers of osteoresorption: DPD/creat.

24 hour production in urine• other lab. exam.: minerals in serum, and urine, TSH, ...• other examination: bone biopsy• FRAX

Bone densitometry

- osteopenia

T-score -1,0 to -2,5

- osteoporosis

T-score ˃ 2,5

T-score (z) is defined:

μ is the mean of the young population;

x is the determined value

σ is the standard deviation of the population.

Basic laboratory screeningBasic screening S-Ca,U-Ca, phosphates, magnesium, urea,

creatinine, protein elfo, KO, FW, ions, KM, glycemia, albumin, AST, ALT, GMT, ALP, TSH, basic urine examination

Renewal markers ALP, osteocalcin, bone isophorm of ALP,PICP, PINP

Serum resorption markers ICTP, CTx, NTx

Urine resorption markers DPD, NTx, CTx

Hormons TSH, PTH, testosterone, and DHEAS men

Vitamin D level 25(OH)D, and 1.25(OH)D over 65 year

Special Estradiol, cortizol, ACTH

Minerals estimation – calcium in serum and urineCalcium is serum is not correlated with the level of bone remodelation.Indication: the aim is to determine possible hypocalcaemia or hypocalcaemia– Ca is decreasing with age in case of men

but not in case of women. Children have higher Ca concentration than adults.

Calcium excretion is not correlated with the level of bone remodelation.Indication: diagnosis of calcium urolithiase, assessment of hyper- and hypocalcaemic syndrome, bowel malabsorption, osteoporosis caused by decrease of the kidney threshold in kidney

Phosphorus in serumPhosphorus in serum is not directly correlated with level of bone remodelling.Indication: Discovery of phosphorus nutrition malabsorption, discovery of hyper or hypo secretion of PTH and phosphate retention in case of kidney disease.

Parathormon

• Indication: suspecting elevated or decreased PTH secretion, at dif. dg. hypercalcaemic, and hypocalcaemic syndromeClinical importance: in case of primary hyperparathyreosis the PTH and calcium concentrations are correlated.

Vitamin D

Vitamin D3 – cholecalciferol (90-95%)

Vitamin D2 – ergocalciferol (5-10%)

25-OH vitamin D2 or D3 – calcidiol

1,25(OH)2 vitamin D – calcitriol

24,25(OH)2 vitamin D

25,26(OH)2 vitamin D

Literature: about 37 metabolites + 64 possible steric isomers

BONE METABOLISMS

(Bone turnover)

DEGRADATION FORMATION

BONE REMODELLING

Bone remodelling cycle

Basic types of bone metabolism markers

• Biochemical markers of bone formation

• Biochemical markers of bone resorption

Biochemical markers of bone formation

Osteocalcin (bone gla - protein)Indication: assessment of the osteoblasts’ activity

Elimination: kidney

S - bone ALPIndication: assessment of the bone creation level

Elimination: ALP from blood is eliminated by liver, not by kidney. Therefore, in case of irreversible kidney failure, ALP is a reliable marker of bone formation.

Biochemical markers of bone formation

Procollagen type I propeptidesAre derived and cleaved from procollagen type I during collagen synthesis, then are delivered into the blood, where they can be measured. Both N-terminal and C-terminal can be used as markers of bone formation.

Procollagen type I N-terminal propeptide (PINP)Indication: is a indicator of bone formationElimination:PINP is eliminated by liver endothelial cells

Biochemical markers of bone resorption

Collagen type I telopeptidesThe telopeptide concentration is independent on the amount collagen in diet. Excreted only during osteoresorption.

Aminoterminal telopeptide NTX (urine, serum)

Carboxyterminal telopeptide CTX - I (urine, serum)Indication: determination of the osteoresorption level

Pyridinoline cross-linkers of collagen - PYD , DPD Indication: determination of the osteoresorption level (alternative to CTX or NTX).

Supplementation and treatment

Treatment1. Common rules - diet, physical activity,

exclusion of long term. mobilisation…

2. Drugs

a) Resorption decrease

calcium, vitamin D, HRT, bisphosphonates,

b) Formation support

fluoride salts, anabolics, parathormon

c) strontium ranelate

d) denosumab

OP Prevention and Treatment Calcium

prevention of negat. calcium balance:

RDA Ca:

- 500 - 800 mg: children - 1000 mg: men and premenop. women - 1500 mg: pregnant and breast-feeding

women - 1500 mg: men 50. y. + postmenop.

women (supplementation is functional mainly 5 y. after menopause)

Vitamin D90% of vitaminu D is synthesized from cholesterol by UV irradiation in skin.

- whole body exposition to sun in summer 15 - 20 min to beginning of erythema

= 10 000 – 20 000 IU

- short term exposition face, arms 10 - 20 min in spring, summer or autumn

= 1000 IU

With age the skin ability to synthesize vitamin D decreases down to ¼.(seniors older than 65 years need, at minimum two times longer expositions).

Vitamin D RDA2011 – Endocrinology society

All population- (IU/day) Risk population- (IU/day)

Age RDA Upper limit RDA Upper limit

0-6 month 600 1000 600-1000 2000

6-12 month 600 1500 600-1000 2000

1-3 years 600 2500 600-1000 4000

4-8 years 800 3000 600-1000 4000

9-18 years 800 4000 600-1000 4000

19-70 year s 800 3000 600-1000 4000

Over 70 year 800 4000 600-1000 4000

Pregnant and breast-feeding

14-18 years 600-800 4000 600-1000 4000

19-50 years 800-1000 4000 1500-2000 10000

Recommended levels 2011:

Category Vitamin D (nmol/l)

Vitamin D (ng/ml)

Deficit < 25 < 10

Insuficience 25 - 50 10 - 20

Sufficiency 50 - 250 20 - 100

Excess 250 - 375 100 - 150

Intoxication > 375 > 150

Drug effects

Drug Resorption Formation

Bisphosphonates ↓ ↓

SERM ↓ (less noticable effect)

Strontium ranelate

↓ ↑

Parathormon ↑

Denosumab ↓

Revise questions

- How osteoporosis is diagnosed?

- What are the markes of osteoformation and osteoresorption?

- What is the RDA for calcium and vitamin D for women and men?

- Which drug is mostly used for osteoporosis treatment?

Practise and reality

Case study no. 1

B.K., female, 1936

OA: ICHS, CHOPN

GA: stp. Mammy ablation, climact. from 52 year, 0 HRT

LA: BP (Bonviva) od 4/09, Calcium, vitamin D

Densitometry: spine - 3.2

coxa - 2.6

Case study no. 1

Analyt 4/09 10/09 6/10 2/11

Ca 2.21 2.41 2.19 2.00 2.05-2.4mmol/l

Vitamin D 10 34.2 53,.4 31.6 > 50 nmol/l

Osteocalcin 26.31 19.43 16.67 13.05 15-46 ug/l

CTx 535.3 303.6 183.9 152.1 ng/l

Case study no. 1

0

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měsíc vyšetření

CTx (ng/l) osteokalcin (µg/l)

Case study no.2

E.Z., female, 1938

OA: DLP, HT,↑KM, cholecystolith.

GA: climact. from 50 year, 0 HRT

stp. Colles. fr. LHK, frequent

fr. UL, LL in climact.

LA: BP (Fosavance), Calcium, vitamin D

Densitometry: spine - 3.3

femur – 2.6

Case study no.2

Analyte 11/09 7/2010 2/2011 Ref.interval

Ca 2.3 2.14 2,.7 2.05 – 2.40

Vitamin D 63.1 41.1 44.6

Osteocalcin 37.71 21.84 55.01 15 - 46

CTx 489 215 714.6

TSH 2.464 2.020 < 0.008 0.350 – 4.8

Case study no.2

0,0082,464

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0 8 15

měsíc vyšteření

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CTx (ng/l) osteokalcin (µg/l) TSH (mIU/l)

Case study no.3

N.B., 1932, female

Transferred from neurology, susp. OP

OA: VAS L5/S1, stp. compr. fr. L5 of older date data, stp.Colles fr. both sides

RTG: stp. broken through of upper spinal disc L5 – stp. compr. fr. of older date, degener. changes

CT: stp. compr. fr. L5 conditional OP

LA: ?

Case study no.3

13.8. 2007

19.7. 2010

29.7. 2010 Ref. interval

Calcium 2.16 2.05-2.4 mmol/l

Phosphate in.

1.04 0.74-1.29 mmol/l

ALP 0.76 0.88-2.35 ukat/l

Osteocalcin 10.49 15-46 ug/l

CTx 63.0 ng/l

PTH 11.16 1.3-7.6 pmol/l

Creatinine 69 42-80 umol/l

25OH D3 52.3 >50 nmol/l

Interfraction-beta,gama

0.057/ 0.022

Case study no.313.8.2007 19.7.2010 29.7.2010 Ref. interval

Calcium 2.16 2.05-2.4

Phosphate in.

1.04 0.74-1.29

ALP 0.98 0.77 0.76 0.88-2.35

Osteocalcin 10.49 15-46

CTx 63,0

PTH 11.16 1.3-7.6

Kreatinin 87 57 69 42-80

25OH D3 52.3

Interfraction-beta,gama

0.066/ 0.022

0.057/ 0.022

Paraprotein IgA lambda

17.6 6.5

Case study no.4

J.P.,1955, female

OA: HT, HLP

GA: stp. HY, has adnexes, climact. from 1991

LA: Rhefluin, Tulip

Transferred to metab. dept. 8/2007 - dyslipoproteinemia.

Case study no.48/07 7/08 11/08 2/09 9/09 12/09 1/10 5/10

Ca 2.66 2.49 2.7 2.53 2.81 2.55 2.61 2.79

OC 34.9 46.3 46.3

CTx 449 812 760

Vit D 23.7 41.8 <10 19.4

P 0.86 0.93

PTH 10.1 9.22 9.53 8.59

Case study no.5

J.R., 1949, female

OA: APPE, CHCE, one-side. ovarektomia 1993, smoking

- exanthema of unknown origin – dermatology dept. from 2004

- occasional dyspepsia – gastroenterology dept. from 2004

- transferred from orthopaedic dept., medication: bisphosphontes (Fosavance), Calcium and Vigantol (vit.D.)

Case study no.5

2006 2007 2008 2009 2010

S-Ca 2.09 2.16 2.14 2.23 2.22

osteocalcin 4.42 10.92 14.09 15.65 12.48

S-CTX 57.1 133.8 202.8 213.1 47.6

25(OH)D3 49.03 66.1 81.5 51.3

Densitometry - year T score

2004 -4.8

2007 -3.0

2009 -2.6

Case study no.5

In 2009 transferred to immunology susp. gluten intoler. Examined hormonal and cell immunity, not checked gluten intolerance. Food allergy not diagnosed. Dietary recommendation 0.

Repeated demand for examination of gluten intolerance - git inconvenience, skin problems – susp.dermatitis herpetiformis During – confirmed 2010.

Case study no.6L.K,1937,male

OA: Ischemia with sy AP, chronic fatigue sy, struma, hypothyreosis, gastritis, kidney cysts, prostatolithiase, pacemaker (1996) for AV block III. degree, glaucoma

NO: lumboischiadic sy with  irritation after L5 bilat.

LA: Tramal, Sirdalud, Atarax, Mesocain ung, Yellon gel,vitaminotherapy, Anavenol…( after transfer ). Local injection, H-mixture, VD infusion.RHB.

EMG: polyneuropathy LL of axonal type with affected sensitive filaments.

In 1999 densitometric measurement, diagnosed osteoporosis,T score –3.99.

Transferred to our dept. 2001.

Densitometry – T score:

12/ 1999 2/ 2002 7/ 2003

-3.99 -3.68 -2.88

Psychologic examination: somatomorphic disorder, secondary hypochondrisation with polymorbidity.

Laboratory results

 

Method 2/2001 3/2002 1/2003 3/2004

S-Ca 2.28 2.28 2.51 2.39

ACP 0.160 0.084 0.082 0.079

ALP 1.06 1.32 1.13

ALPK 0.27 0.22 0.22 0.26

OC <1.0 3.4 3.4 4.33

Vit. D 63 65

S-CTX 86.7 101.3 87.9

U-DPD 5.48 5.01 5.53 5.33

U-Ca 6.0 4.3 3.8 2.8

Case study no.7

V.T., 1961, femaleOA: 0, 169cm, 72kgRA: 0GA: regular period, 3 children, antic. 0LA: FerronatNO: Weight loss 15kg in last month, back pain, myalgia, snore, subfebrile to febrile, fatigue. Transferred to our dept. after hospitalization in general medicine dept. (febrile and fatigue) and neurology dept. (muscle problems) susp. osteoporosis.

Basic biochemistry screening, KO, TH and PTH, lipid profile without any reported difference from normal range.

Basic biochemistry screening repeated.

Method Result Ref. interval

S- Ca 2.48 2.05-2.54

Ioniz. Ca 1.23 1.13-1.32

ALPK 0.31 0.19-0.51

ACP 0.085 0.083-0.139

TSH 1.6 0.36-4.8

cholesterol 4.7 3.4-5.2

Fe 12.1 6.6-12.8

OC 13.3 4.6-10.2

Albumin 42.9 35-53

U-Ca 11.3  

U-DPD 9.6  

PTH 40 (!)  

Thank you for your attention