MSK Diseases 2 Flashcards

Question

What is the healing potential for Tendon

Answer 1

* Depend upon Grade of injury. * Repairs weakest at 7 - 10 days. * Regain most of original strength at 21 - 28 days. * Maximum strength at 6 months

Answer 2

1. Promote early function. 2. Increase ROM. 3. Encourage weight bearing. 4. Improve muscular strength/endurance and control.

Answer 3

* Outer= **cortex,** inner=**trabecular** * ECM= **osteoclasts, osteoblasts and osteocytes** * Bone is layer down in lamellae * Osteon-= **concentric lamellae with central haversian canal** * Volkmann's cannal= **in between osteons** * Woven bone= **immature bone**

Answer 4

* Support * Movement * Protects organs * Hematopoiesis * Mineral homeostasis

Answer 5

RANKL-RANK-OPG: RANK binds to osteoclast precursor RANKL binds to RANK-\>stimulates NFkB-\> activates osteoclast formation OPG inhibits RANK/RANKL binding-\> inhibiting osteoclast formation

Answer 6

RANK binds to extracellular vesicle-\> attaches to RANKL on osteoblast-\> stimulates RUNX2-\> osteogenesis Sclerostin inhibits Wnt-\> inhibiting osteogenesis

Answer 7

calcium and phosphate

Answer 8

Ca2+ regulated by **chief** cells of the Parathyroid gland

Answer 9

If decrease in Ca2+-\> PTH-\> decrease PO4 & increase Ca2+

Answer 10

binds to osteoblasts-\> promotes osteoclastogenesis via RANKL upregulation-\> excess Ca2+ ( CKD -\> 2dary hyperparathyroidism) stimulates production of calcitriol-\> promotes synthesis of calbindin in intestinal epithelial cells-\> increased absoprtion of Ca2+ in GI tract promotes Ca2+ reabsorption in kidneys

Answer 11

sclerostin

Answer 12

osteoblastogenesis + inhibits RANKL-\> no osteoclastogenesis

Answer 13

Oestrogen deficiency-\> osteoclastogenesis, no inhibition of sclerostin-\> inhibited osteoblastogenesis Perimenopause/Childbearing-\> estrogen-\> osteoblastogenesis Postmenopausal-\> problems start – osteoporosis/ osteopenia

Answer 14

* Porous bones- reduced trabecular bone à increased risk of fracture (50 y/o female = 50% lifetime risk of fragility fractures) * resorption\>formation * Most common metabolic bone disease

Answer 15

* Affects women more after menopause à less oestrogen àosteoclastogeneis + uninhibited sclerostin à deceased osteoblastogenesis * Affects old people more (senile osteoporosis) à impaired osteoblast function à more resorption * Older age * Female * Reduced mobility and activity * Low BMI (\<18.5 kg/m2) * Rheumatoid arthritis * Alcohol and smoking * Long term corticosteroids. NICE suggest the risk increases significantly with the equivalent of more than 7.5mg of prednisolone per day for more than 3 months) * Other medications such as SSRIs, PPIs, anti-epileptics and anti-oestrogens

Answer 16

•Determinants of peak bone mass: genetics, body weight, sex hormones, diet, exercise Determinants of bone loss: sex hormone deficiency, genetics, diet, immobility, diseases, drugs (corticosteroids, aromatase inhibitors, glitazones

Answer 17

* height loss * thoracic kyphosis or lumbar lordosis * protuberant abdomen * decreased lung capacity * early satiety, weight loss, oesophageal reflux

Answer 18

-DEXA scan * Compares pts bone density to that of a normal adult * Produces a T-score = 2.5 è osteoporosis - X ray - PTH, TFTs, vit D, urinary calcium (24hr), bone turnover markers- CTX & P1NP

Answer 19

**Antiresorptive:** * Bisphosphonates eg alendronic acid * Anti-RANKL ab eg Denosumab **Anabolic:** * recombinant PTH eg teriparatide * Anti-sclerostin Ab eg Romosozumab

Answer 20

* Disorder of bone remodelling – focally increased and disorganised bone turnover * driven by abnormal osteoclasts à increased and haphazard osteoblast activity à formation of poor quality woven bone Paget’s disease of bone refers to a disorder of bone turnover. There is excessive bone turnover (formation and reabsorption) due to excessive activity of both **osteoblasts and osteoclasts.** This excessive turnover is not coordinated, leading to patchy areas of high density (sclerosis) and low density **(lysis)**. This results in enlarged and misshapen bones with structural problems that increase the risk of **pathological fractures**. It particularly affects the **axial skeleton** (the bones of the head and spine).

Answer 21

**Genetics** * Fx * Mutations- SQSTM1 most common * Ethnicity **Environmental** * Involvement of paramyxovirus * Mechanical loading of affected bone * Poor nutrition in childhood

Answer 22

* Early – asymptomatic * Bone Pain= bone impinges on nerves * Overgrowth of bone - Facial deformity- leontiasis - Hearing loss- impingement on auditory nerve - Vision loss – impingement on optic nerve * Osteosarcoma à pagets sarcoma * Kyphosis * Lower limb muscle weakness * Pelvic asymmetry * Bow legs * Arthritis * Fractures * Bone deformity * Fractures * Hearing loss can occur if it affects the bones of the ear

Answer 23

* Elevated ALP (isolated) * Elevated bone turnover markers à P1NP and CTX * X ray- osteolysis, osteosclerosis, chaotic bone architecture, bone expansion and deformity * Radionucleotide bone scan- increase in tracer uptake in affects bones

Answer 24

•Bisphosphonates eg Zoledronate and risedronate – they cause osteoclast dysfunction/death Other measures include: * NSAIDs for bone pain * Calcium and vitamin D supplementation, particularly whilst on bisphosphonates * Surgery is rarely required for fractures, severe deformity or arthritis

Answer 25

* decreased serum calcium/phosphate à widening and delay of mineralisation of growth plates in bones * Associated with osteomalacia

Answer 26

•Causes bowing deformity of bones, rachitic rosary, Harrison sulcus, widened wrist

Answer 27

* Widening gair/ delay in walking * Bone pain, fatigue * Fractures * Short stature * Tetany/ seizures * Cardiomyopathy

Answer 28

Vitamin d dependent rickets Hypophosphatemic rickets

Answer 29

**Caused by** * Deficiency in 1 alpha hydroxylase * Inactivating mutations in the vit D receptor **VDDR type I:** * Deficiency in 1-alpha hydroxylase ( converts into calcitriol) * 25(OH) will be normal/high but 1,25(OH) will be low **VDDR type II:** * Inactivating mutations in Vit D receptor- VDR * Both 25(OH), 1,25(OH) will be normal or high

Answer 30

* Excessive renal phosphate losses * Low serum phosphate for normal bone mineralisation * Excess in FGF23 expressed by osteocytes * PHEX, DMP1 normally inhibit FGF23-\> mutations increase FGF23 * _Subtypes:_ - XLH: X-linked, PHEX- more common - ADHR:AD, FGF23 - ARHR:AR, DMP1

Answer 31

* Softening of bones dues to defective mineralisation of newly formed bones * Mainly caused by vit D deficiency, Hypophosphatemia, inhibitors of mineralisation

Answer 32

* Bone pain * Bone tenderness * Fractures * Muscular weakness * Malaise * Tetany * Fatigue Looser zones are fragility fractures that go partially through the bone.

Answer 33

* Vitamin D and calcium * Active vit D metabolites (+/- calcium infusions) for VDDR * Phosphate supplements for hypophosphataemic rickets, plus active vitamin D metabolites * Burosumab (anti FGF23 ab) for children with XLH

Answer 34

The FRAX tool gives a prediction of the risk of a **fragility fracture** over the next 10 years. This is usually the first step in assessing someone’s risk of **osteoporosis.** It involves inputting information such as their age, **BMI, co-morbidities, smoking, alcohol and family history.** You can enter a result for bone mineral density (from a DEXA scan) for a more accurate result but it can also be performed without the bone mineral density. It gives results as a percentage 10-year probability of a: * Major osteoporotic fracture * Hip fracture

Answer 35

Bone mineral density (BMD

Answer 36

Assessing For Osteoporosis The first step is to perform a FRAX assessment on patients at risk of osteoporosis: * Women aged \> 65 * Men \> 75 * Younger patients with risk factors such as a previous fragility fracture, history of falls, low BMI, long term steroids, endocrine disorders and rheumatoid arthritis.

Answer 37

FRAX outcome without a BMD result will suggest one of three outcomes: * Low risk – reassure * Intermediate risk – offer DEXA scan and recalculate the risk with the results * High risk – offer treatment FRAX outcome with a BMD result will suggest one of two outcomes: * Treat * Lifestyle advice and reassure

Answer 38

Lifestyle Changes: Vitamin D and Calcium:Calcichew-D3, which contains 1000mg of calcium and 800 units of vitamin D (colecalciferol). Bisphosphonates are the first-line treatment for osteoporosis. * Alendronate 70mg once weekly (oral) * Risedronate 35 mg once weekly (oral) * Zoledronic acid 5 mg once yearly (intravenous)

Answer 39

Patients with darker skin require a longer period of sun exposure to generate the same quantity of vitamin D. A standard diet contains inadequately levels of vitamin D to compensate for a lack of sun exposure. Reduced sun exposure without vitamin D supplementation leads to deficiency. Patients with malabsorption disorders (such as inflammatory bowel disease) are more likely to have vitamin D deficiency. The kidneys are essential in metabolising vitamin D to its active form, therefore vitamin D deficiency is common in chronic kidney disease. Vitamin D is essential in calcium and phosphate absorption from the intestines and kidneys. Vitamin D is also responsible for regulating bone turnover and promoting bone reabsorption to boost the serum calcium level. Inadequate vitamin D leads to a lack of calcium and phosphate in the blood. Since calcium and phosphate are required for the construction of bone, low levels result in defective bone mineralisation. Low calcium causes a secondary hyperparathyroidism as the parathyroid gland tries to raise the calcium level by secreting parathyroid hormone. Parathyroid hormone stimulates increased reabsorption from the bones. This causes further problems with bone mineralisation.

Answer 40

Serum 25-hydroxyvitamin D is the laboratory investigation for vitamin D. The interpretation of the results is as follows: * \<25 nmol/L – vitamin D deficiency * 25 – 50 nmol/L – vitamin D insufficiency * 75 nmol/L or above is optimal Other investigation results include: * Serum calcium is low * Serum phosphate is low * Serum alkaline phosphatase may be high * Parathyroid hormone may be high (secondary hyperparathyroidism) * Xrays may show osteopenia (more radiolucent bones) * DEXA scan shows low bone mineral densit

Answer 41

Bone enlargement and deformity * “Osteoporosis circumscripta” describes well defined osteolytic lesions that appear less dense compared with normal bone * “Cotton wool appearance” of the skull describes poorly defined patchy areas of increased density (sclerosis) and decreased density (lysis) * “V-shaped defects” in the long bones are V shaped osteolytic bone lesions within the healthy bone Biochemistry * Raised alkaline phosphatase (and other LFTs are normal) * Normal calcium * Normal phosphate

Answer 42

* Osteogenic sarcoma (osteosarcoma) * Spinal stenosis and spinal cord compression