Osteomalacia

Osteomalacia
Dr Sanjeev Patel
COPYRIGHT Dr S Patel
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Objectives
Vitamin D physiology Vitamin D &
Bone Falls Pain ImmuneCOPYRIGHT regulation Dr S Patel
Vitamin D
Steroid hormones
Derivatives of cholesterol Fat soluble lipids Circulate bound to plasma proteins Not stored in cells Rate of secretion = rate of synthesis Steroid hormones are derived from COPYRIGHT Dr S Patel cholesterol by a biochemical reaction series
Steroid hormone structure

Steroids
The central core of this molecule, consisting of four fused rings, is shared by all steroids including cholesterol and steroid hormones
C A B Basic 4 carbon ring structure of steroids
COPYRIGHT Dr S Patel D
Synthesis of Vitamin D
Mainly synthesised from the effect of UV light in skin 10 % from diet
(fatty fish and dairy products Dr S Patel that have COPYRIGHT been supplemented)
Factors influencing vitamin D synthesis by the skin

Sunlight exposure
Latitude Clothing Sunblocks Skin pigmentation COPYRIGHT Dr S Patel
Diet has a minor role

Sunlight and vitamin D

15 minutes daily exposure on face and hands between 11am and 2 pm is adequate Seasonal variation Sunblock (> factor 8) reduces efficiency of skin by 95 %
25 versus 1,25 vitamin D

25-vitamin D reflects skin synthesis and dietary intake 1,25 reflects hydroxylation in the kidneys 1,25 is more than 25-vit D there is COPYRIGHT Dr Sbut Patel much more 25-vitamin D to have a biological effect
Actions of vitamin D
Major action
Increases absorption of calcium form GIT
Other actions
Bone resorption COPYRIGHT Dr S Patel Cell differentiation Immune regulation ?
Parathyroid hormone
Secreted by parathyroid glands
Primary function is Dr S Patel COPYRIGHT calcium homeostasis
Parathyroid hormone
Vitamin D endocrine system
Vitamin D and bone
Normal bone
COPYRIGHT Dr S Patel 3
There are 3 elements in the slides - bone trabeculae, adipose cells, and blood cells(1)(2). The trabeculae are elongate and stain eosinophilically. Trabecular bone under polarised light showing lamellar arrangement of collagen
Osteomalacia
Osteomalacia in medullary bone, non-decalcified section. There is a marked increase in red-staining, non-calcified osteoid matrix.
Normal
Osteomalacia
Osteoporosis v. osteomalacia
Normal Osteoporosis Osteomalacia
Bone amount Mineralisation Bone turnover Bone strength
Normal
Reduced
Normal
Normal Normal COPYRIGHT Dr Normal Normal
S Patel Reduced
Increased Reduced
Increased Reduced
Bone mineralisation
Bone matrix is physiologically mineralised with tiny crystallites of a basic carbonate-containing calcium phosphate (hydroxyapatite)
COPYRIGHT Dr S Patel Two mechanisms described
Calcified cartilage and woven bone Lamellar bone

Mineralisation in woven bone

Matrix vesicles from osteoblasts Membrane bound bodies that exocytose and migrate to extracellular matrix space Nidus for crystal formation and COPYRIGHT Dr S Patel crystallisation
Mineralisation in lamellar bone

Occurs around non-collagenous proteins rather than Type I collagen itself Unclear what the driving force is Purified collage seems to be a poor initiator of crystal deposition
Control of mineralisation
Concentration of mineral ions
Calcium Phosphate
Inhibitor molecules
pyrophosphate
Effects of vitamin D defiency

Low Vit D levels
Increased bone turnover Increased loss of phosphate
Ca P
AlkP & PTH
Causes of nutritional osteomalacia

Vit D deficiency
Lack of adequate sunlight Low intake of Vit D GI diseases
Calcium deficiency
Dietary
Phosphate deficiency
TPN Chronic phosphate binder therapy

Classification of vitamin D status

Vitamin D deficiency
Frankly low Vit D and high PTH
Vitamin D insufficiency
Low / normal Vit D and slightly raised PTH
Vitamin D replete
Normal Vit D and PTH
Clinical features of osteomalacia

Bone pain Proximal weakness Symptoms from hypocalcaemia Deformity Fracture
Investigations
Suggestive of osteomalacia
Low calcium Low phosphate Low Vit D Raised PTH Dr S Patel X-ray / COPYRIGHT bone scan abnormalities
To investigate underlying pathology

Loosers zones
Osteomalacia: Bone scan
Management
Treatment of underlying cause as appropriate Calcium supplementation Vitamin D supplements
Parent vitamin D (oral or I.m.) COPYRIGHT Dr S Patel Activated vitamin D (oral)
Osteoporosis and falls

Vitamin D deficiency causes myopathy Vitamin D supplements in older people
Reduces secondary HPTH Improves BMD ReducesCOPYRIGHT incidence of falls Dr S Patel
How best to supplement vitamin D ?

Vitamin D and chronic pain

Osteomalcia classically causes chronic bone pain What about vitamin D insufficiency ?

88 % of Danish women of Arab descent who presented with muscle pains and weakness were vitamin D deficient
Glerup et al 2000

Studied 150 consecutive patients with persistent nonspecific musculoskeletal pain Found that all had low levels of COPYRIGHT Dr S Patel Vitamin D
Plotnikoff, Quigley 2003 Mayo Clin Proc
Relationship between Vit D and pain

Normal Vit D No contribution
Insufficiency
Nonspecific pain
Deficiency
Osteomalcic pain
Relationship between Vit D and pain

Problems ? No controls No intervention COPYRIGHT Dr S Patel
Vitamin D and immune regulation

In vitro data that 1,25 vit D inhibits T cell proliferation and decreases the production of Th 1 cytokines IL-2, IFN- and TNF- (Lemire 1992). In vivo work that 1,25 vit D supplementation prevents experimental autoimmune encephalitis (a murine model used to determine the efficacy of drugs for therapy of multiple sclerosis) and COPYRIGHT Dr S Patel inflammatory arthritis (Cantorna et al 1996; Cantorna et al 1998).
Vitamin D - summary
Low levels are common and cause
Osteomalacia Osteoporosis Falls Dr S Chronic COPYRIGHT pain syndromes ?Patel Immune dysfunction ?

Osteomalacia

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Osteomalacia

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Osteomalacia

Steroid hormone structure

Factors influencing vitamin D synthesis by the skin

Diet has a minor role

Sunlight and vitamin D

25 versus 1,25 vitamin D

Primary function is Dr S Patel COPYRIGHT calcium homeostasis

Vitamin D endocrine system

Vitamin D and bone

Bone amount Mineralisation Bone turnover Bone strength

Normal Normal COPYRIGHT Dr Normal Normal

Calcified cartilage and woven bone Lamellar bone

Mineralisation in woven bone

Mineralisation in lamellar bone

Effects of vitamin D defiency

AlkP & PTH

Causes of nutritional osteomalacia

TPN Chronic phosphate binder therapy

Classification of vitamin D status

Clinical features of osteomalacia

To investigate underlying pathology

Osteomalacia: Bone scan

Osteoporosis and falls

How best to supplement vitamin D ?

Vitamin D and chronic pain

Vitamin D and chronic pain

Vitamin D and chronic pain

Relationship between Vit D and pain

Relationship between Vit D and pain

Vitamin D and immune regulation

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