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MENTI: 69839531 Qais Mohammad qm420@ic.ac.uk Endo & Bones MedEd Y3 Written Exam Lectures 2025 1 SESSION CONTENT ü Endo: ü Malignancy: ü Bones: ü Hyperparathyroidism ü Hypercalcaemia of ü Paget’s Disease (Primary, secondary, malignancy ü Osteoporosis tertiary) ü Metastatic disease ü Hypoparathyroidism (carcinoid syndrome) ü Pathological fracture ü Osteomalacia 2 Learning Objectives Malignancy: 1. Identifyandinterpret clinical data(fromhistory, examinationand ü Endo: investigations) tomake adiagnosis of eachcondition ü Bones: ü2. Formulate amanagement planfor eachcondition, recognisingthe risks andease (Primary, secondary, benefits of treatments ü Osteoporosis tertiary) ü Hypoparathyroidismlaboratory sciences toinformthe diagnosis, management andprognosis of eachconditionHypercalcaemiaof malignancy ü Osteomalacia Metastaticdisease(carcinoidsyndrome) Pathological fracture 3 PTH Secreted as pre-pro-PTH by chief cells in the parathyroid glands. G-protein coupled calcium sensing receptor on chief cells detects changes in circulating calcium conc. PTH levels ∝ 1/[Ca ]+ Adapted from Prof Niam Martin’s lecture, Regulation of Ca and PO4 Check this reference 4PTH action and regulation Adapted fromProf NiamMartin’s lecture, Calciumdysregulation 5 Hyperparathyroidism Overview: ↑ PTH levels à↑ [Ca ] and ↓ [P4 ] F>M(3:1), most cases occur >50 yrs old Causes: Primary HPT: Secondary HPT: Tertiary HPT: Parathyroid gland Malnutrition Chronic increase in adenoma (benign) PTH secondary to Vit D deficiency CKD CKD Hyperplasia of parathyroid glands Increased resorption from the bone and more excretion of PO4 from the kidney Secondary HPT – chronic low levels of Ca -> high PTH as a compensatory mechanism CKD: ↓ Kidney function → ↓ Active vitamin D (calcitriol) → ↓ Calcium absorption ↓ Kidney function → ↑ Phosphate retention → ↓ Free calcium ↓ Calcium & ↑ Phosphate → ↑ PTH release → Secondary Hyperparathyroidism 6 HPT – Clinical features • Primary HPT: • Anorexiaia &Polyuria • Nausea • Constipation • bone pain(esp. back pain) • renal stones • lowmood 💡 Syx of Hypercalcaemia: bones, stones, groans &moans Most patients are asymptomatic • Secondary and Tertiary HPT: Syx relatedto the underlying cause (renal failure, bone pain, fractures) 7 HPT – making a diagnosis Investigations: • Serum Ca2+ • PTH • Vit D • PO 4 • US to check for Parathyroid adenoma • DEXA Scan Primary HPT: Secondary HPT: Tertiary HPT: ↑ PTH levels ↑ PTH levels ↑ ↑ PTH levels 2+ 2+ 2+ ↑ [Ca ] ↓ à[Ca ] ↑ [Ca ] ↓ [PO 4- ↑ [PO 4- ↑ [PO 4- ↑àVit D ↓Vit D ↓Vit D 8 HPT – management • Primary HPT: • Total parathyroidectomy (definitive management) • Calcimimetics (Cinacalcet) aredrugs that inhibit PTHrelease • IVFluids for treat hypercalcaemia • Secondary HPT: • treat underlying cause(ie. CKD, Vit Ddeficiency) • Tertiary HPT: • Parathyroidectomy 9 SBA 1 A65-year-oldmanwitha historyof chronic kidneydisease (CKD) stage 4presents withbone painandpruritus. Bloodtests reveal: • Calcium: 2.0mmol/L (Low) • Phosphate: 1.9mmol/L (High) • ParathyroidHormone (PTH): Elevated • VitaminD(Calcitriol): Low Whichof the followingis the most likely mechanismleadingtohis elevatedPTHlevels? A. Anincreasedphosphate excretionleadingtohypocalcemia B. Excessive calciumloss inthe urine due toCKD C. ImpairedvitaminDactivationandphosphate retention D. Direct stimulationof PTHbyexcess calcium E. Increasedcalciumabsorptionfromthe gut Answer: C) Impaired vitamin D activation and phosphate retention Explanation: In CKD, the failing kidneys are unable to: 1.Activate vitamin D → ↓ Calcitriol → ↓ Calcium absorption from the gut → Hypocalcemia 2.Excrete phosphate → Hyperphosphatemia → Phosphate binds to calcium, further lowering ionized calcium levels 3.Hypocalcemia & hyperphosphatemia stimulate parathyroid hormone (PTH) release, leading to secondary hyperparathyroidism (SHPT). 10 SBA 2 A65painandpruritus. Bloodtests show:ic kidneydisease (CKD) stage 4presents withbone • Calcium: 2.0 mmol/L (2.2–2.6 mmol/L) • Phosphate: 1.8 mmol/L (0.8–1.5 mmol/L) • Parathyroid Hormone (PTH): 150 pmol/L (1.6–6.9 pmol/L) Whichtype of hyperparathyroidismdoes this patient most likelyhave? A. Primaryhyperparathyroidism B. Secondaryhyperparathyroidism C. Tertiaryhyperparathyroidism D. Parathyroidcarcinoma E. Familial hypocalciuric hypercalcemia Correct answer: B) Secondary hyperparathyroidism •Low calcium, high phosphate, and high PTH are classic for secondary hyperparathyroidism, most commonly due to CKD. •CKD leads to reduced vitamin D activation and phosphate retention, causing hypocalcemia, which stimulates PTH secretion. Why not the others? •A) Primary hyperparathyroidism: High PTH & calcium, but low phosphate ❌ •C) Tertiary hyperparathyroidism: High PTH & calcium due to autonomous gland function ❌ •D) Parathyroid carcinoma: Extremely high PTH & calcium, rare ❌ •E) Familial hypocalciuric hypercalcemia: Mildly high calcium & PTH, low urine calcium ❌ 11 Hypoparathyriodism • Overview: • Deficiencyof PTHsynthesis andsecretion • ↓[Ca ] ↑[PO ] 3- 4 • Aetiology • Postoperative – thyroidectomy/parathyroidectomy • Autoimmune • Non-autoimmune (Wilsondisease, Haemochromatosis) • DiGeorge syndrome Psuedohypoparathyroidism: • Target organs don’t respondtonormal levels of PTH • Short stature andfingers, hypercalcaemic symptoms, Vit Ddeficiency Wilson’s – Copper accumulates in gland -> damage à reduce hormone production Haemochromatosis – excess iron à deposited in gland à fibrosis à gland dysfunction à reduce hormone DiGeorge’s – 22q11.2 deletion – parathyroid hypoplasia – agenesis à hypoparathyroidism 12 Hypoparathyriodism – diagnosis Clinical features Hypocalcaemia = increasedneuromuscular excitability • Tetany→muscle twitching, crampingandspasm • Paraesthesia, Numbness, Tingling • Poor Memory, SlowedThinking • Malnutrition, Malabsorption, Diarrhoea • Arrhythmias →prolongedQTinterval 💡 Hypocalcaemia = CATs go Numb →Convulsions, Arrhythmias, Tetany, Paraesthesia 13 Hypoparathyriodism – diagnosis • Chvostek’s Sign(ch = cheek) → •TrousseauSign(t = tighten contraction of facial muscles cuff) →painful clasping when facial nerveis tapped in response when BP cuff is front of theear inflated abovesystolic BP Low Calcium à increased neuromuscular excitability à Muscle spasms 14 Hypoparathyriodism – Investigations • PTH- low • SerumCalcium→low • (andnormal ALP) • SerumPhosphate →high • ECG→isolatedprolongedQT interval • (predisposes toTDP) indicates severelife-threatening hypocalcaemia • SerumAlbumin →normal • lowalbuminwill give afalsely low serumcalcium When calcium is low, the repolarization phase of the heart's electrical cycle is delayed, which extends the QT interval. This prolonged interval increases the risk of arrhythmias, including torsades de pointes (TDP). Hypocalcaemia à PLQTi à Abnormal rhythms à TDP à Cardiac arrest/low BP/dizziness/fainting/sudden death Calcium + magnesium to stablise the heart Calcium stabilise the heart's electrical activity, and when it's low, the heart takes longer to reset after each beat. This delay increases the risk of abnormal heart rhythms, like TDP, as the heart's electrical signals become more prone to irregularities. Calcium binds to albumin in the blood. When albumin is low, there is less bound calcium, but the free (active) calcium may remain normal. 15 Hypoparathyriodism – Management Supplementation: • IVor Oral Calcium • Calcitriol (formof Vit D) Regular Monitoring – Ca and PTHlevels Complications →cataract, hypercalcaemia, renal insufficiency, renal stones, neurological and neuropsychiatric sequelae Prognosis →depends on aetiology and severity Complications: Cataracts: Low calcium can lead to calcium deposition in the eye lens, causing cataracts. Hypercalcemia: Inappropriate calcium supplementation or uncontrolled calcium metabolism may cause hypercalcemia. Renal insufficiency: Chronic low calcium levels lead to kidney damage, reduced glomerular filtration, and impaired renal function. Renal stones: High phosphate and calcium levels may lead to the formation of kidney stones. Neurological/neuropsychiatric sequelae: Low calcium levels cause excitability in nerves and muscles, leading to seizures, anxiety, depression, and cognitive issues. 16 Psuedoypoparathyriodism Definition:ement Differential Diagnosis: Araregenetic disorder wheretarget respondto PTHdespitenormal oril to • Hypoparathyroidism(lowPTH) highlevels. • Vitamin Ddeficiency Cause: • GNAS1gene mutation→Defective • Chronic kidney disease PTHreceptor signalling Investigations: Clinical Features: • ↓Calcium, ↑or normal PTH • H• Numbness, muscle cramps, seizures Management: • Chvostek’s &Trousseau’s signs • Calcium&Vitamin D • Skeletal abnormalities: • Short stature, short 4th&5th supplementation metacarpals 17 SBA 3 A45-year-oldmanwitharecent diagnosis of hypoparathyroidismpresents withmuscle cramps andnumbness inhis fingers. Onexamination, he demonstrates apositive Chvostek's signandTrousseau's sign. Whichof the followingbest explains why these signs are present inthis patient? A. Increasedparathyroidhormone (PTH) levels leadtohyperexcitabilityof nerves B. Decreasedserumcalciumlevels cause increasedneuromuscular excitability C. Elevatedphosphate levels directlystimulate nerve activity D. Increasedmagnesiumlevels leadtomuscle spasms E. LowvitaminDlevels cause decreasednerve conductionvelocity B) Decreased serum calcium levels cause increased neuromuscular excitability. Explanation: Chvostek's and Trousseau's signs are signs of hypocalcemia, which occurs due to hypoparathyroidism. Low calcium levels cause increased neuromuscular excitability, leading to muscle spasms and abnormal responses like Chvostek's (tapping the facial nerve causes twitching) and Trousseau's (carpopedal spasm induced by inflating a blood pressure cuff). 18 SBA 4 A30-year-oldwomanpresents withmuscle cramps, fatigue, andtinglinginher hands and feet. Onexamination, she has Chvostek’s signandTrousseau’s sign. Her laboratoryresults showthe following: • Serum calcium: 7.8 mg/dL (normal range: 8.5–10.2 mg/dL) • Serum phosphate: 6.2 mg/dL (normal range: 2.5–4.5 mg/dL) • Serum PTH: 120 pg/mL (normal range: 10–65 pg/mL) • Serum creatinine: Normal Hxof short stature anda roundface. Nohxof kidneydisease or other chronic conditions is noted. Whichof the followingis the most likelydiagnosis? A. Hypoparathyroidism B. Pseudohypoparathyroidism C. Primaryhyperparathyroidism D. VitaminDdeficiency E. Chronic kidneydisease-relatedhypocalcaemia B A) Hypoparathyroidism: In hypoparathyroidism, PTH levels are typically low due to impaired production by the parathyroid glands. This patient has elevated PTH levels, ruling out hypoparathyroidism. B) Pseudohypoparathyroidism: This condition occurs due to resistance to PTH at the level of target tissues (such as bone and kidney), despite normal or elevated PTH levels. In pseudohypoparathyroidism, the body’s tissues do not respond to PTH, leading to hypocalcemia and elevated phosphate levels, even though the PTH level is elevated. This patient’s elevated PTH along with low calcium and high phosphate is characteristic of pseudohypoparathyroidism. Additionally, the patient has physical features like short stature and a round face, which are commonly associated with Albright’s hereditary osteodystrophy, a subtype of pseudohypoparathyroidism. C) Primary hyperparathyroidism: In primary hyperparathyroidism, calcium levels are typically elevated, not low, and PTH is also elevated. This patient’s low calcium rules out this diagnosis. D) Vitamin D deficiency: Vitamin D deficiency can lead to low calcium and elevated PTH, but typically, vitamin D deficiency would also show low phosphate levels, not elevated ones. This patient’s high phosphate is inconsistent with vitamin D deficiency. E) Chronic kidney disease-related hypocalcemia: Chronic kidney disease typically 19leads to low calcium and elevated phosphate, but this patient’s normal creatinine levels rule out kidney disease. 19 Osteomalacia Overview: • Osteomalacia: Bonesoftening duetolowvitaminD, leading to reducedbone mineralisation. Causes: • VitaminDDeficiency: Lowsunlight, poor diet, malabsorption (coeliac, pancreatitis) • Defective VitaminDMetabolism: Liver cirrhosis, CKD • Drugs: Anticonvulsants How do Anticonvulsants cause osteomalacia? Anticonvulsants like phenytoin and phenobarbital can cause osteomalacia by increasing liver enzymes, which accelerate the breakdown of vitamin D. This leads to low levels of active vitamin D, impairing calcium and phosphate absorption, resulting in weakened bones. 20 Osetomalcia Clinical Features: • Bonepain &tenderness • Pathological fractures (femoral neck) • Proximal muscleweakness →waddlinggait • Hypocalcaemic symptoms: Tetany, muscle twitching, arrhythmias Investigations: • ↓Vitamin D, ↓Calcium, ↓Phosphate • ↑ALP, ↑PTH(secondary hyperparathyroidism) • X-ray: Looser zones (pseudofractures) Psuedofractures: incomplete fracture – weakened bone due to defective mineralization – indicates bone softening 21 Osteomalacia Differential diagnosis: Management: Complications: • Rickets • Lifestyleadvice – safe • Pseudofractures • Primary sunexposure • Hypercalcaemia hyperparathyroidism • VitaminD • Secondary supplementation hyperparathyroid • Bone metastases (Ergocalciferol/Cholecal ism • Osteoporosis ciferol) • Paget’s disease • Calcium– if dietary intake is low • Management of underlyingcause •Loading dose vitamin D should be prescribed with approximately 300,000 IU given in total over 6-10 weeks (either weekly or daily) •After this is completed, maintenance vitamin D (800-2000 IU per day) should be continued •Patients with chronic kidney disease may require alfacalcidol rather than calciferol (due to reduced activity of 1-alpha hydroxylase which activates vitamin D) 22 SESSION CONTENT ü Endo: ü Malignancy: ü Bones: ü Hyperparathyroidism ü Hypercalcaemia of ü Paget’s Disease (Primary, secondary, malignancy ü Osteoporosis tertiary) ü Metastatic disease ü Hypoparathyroidism (carcinoid syndrome) ü Pathological fracture ü Osteomalacia 23 Hypercalcaemia of malignancy Overview: • ElevatedCa >2.6mmol/L due tocancer Classification: • Mild(2.6-3.0mmol/L) – Minimal symptoms • Moderate(3.0-3.5mmol/L) – Maybesymptomatic • Severe (>3.5mmol/L) – Highriskof complications Three mainmechanisms: 1.Humoral Hypercalcaemia(80%) – Tumour secretes PTHrP(e.g., SCC, renal, breast, ovariancancer)💡 2.Local OsteolyticHypercalcaemia – Bone metastases activate osteoclasts (e.g., multiple myeloma, breast cancer) 3.Calcitriol-MediatedHypercalcaemia – Tumour produces calcitriol (1,25(OH)₂D) (e.g., Hodgkin&Non-Hodgkinlymphoma) 24 Hypercalcaemia of malignancy Symptoms: Management: "Stones, Bones, Groans, Moans" • IVSaline – reversedehydration • Polyuria, Polydipsia • IVBisphosphonates (or Denosumab) – • Fatigue, Confusion, Depression Inhibits osteoclast activity • Constipation, Nausea, BonePain • Treat Underlying Malignancy • Stopcontributing meds e.g. thiazide Investigations: diuretics • ↑SerumCalcium, ↓PTH • Steroids – Vit Dmediateddueto • ↑PTHrP(humoral hypercalcaemia) Lymphoma Complications: • ↑Calcitriol (lymphoma-related • AcuteKidney Injury (AKI) hypercalcaemia) • Coma • ECG→Short QTinterval • AcutePancreatitis PTHrP - (Parathyroid Hormone-related Peptide) Bisphosphonates – lowers Ca2+ Thiazide – increase renal Ca reabsorption in DCT Steroids – suppress 1α-hydroxylase activity in lymphoma cells, reducing the conversion of 25(OH)D to active calcitriol (1,25(OH)₂D). This lowers intestinal calcium absorption and decreases serum calcium levels. 25 Metastatic disease – Carcinoid syndrome Overview: Investigations: A set of symptoms caused by NETs that • 24hr urinary 5-HIAA secreteserotonin &other vasoactive (metaboliteof serotonin) substances – most caused by liver • CT/MRI – to locateprimary metastases tumour Commonest primary sites include: Management: • GIT tumours • Octreotide – Somatostatin • Lung tumours analogue Clinical features: • Surgical resection – primary Flushing, diarrhoea, wheeze, weight loss, tumour or liver metastases right-sided HF • Radio Ablation/Chemo Carcinoid syndrome occurs when a neuroendocrine tumor (usually from the small intestine) secretes serotonin and other vasoactive substances into the bloodstream, bypassing liver metabolism. It typically manifests with: •Flushing (episodic, red skin, especially face/neck) •Diarrhea (watery, secretory) •Wheezing (bronchospasm) •Right-sided heart disease (valvular fibrosis, tricuspid regurgitation, pulmonary stenosis) •Pellagra-like symptoms (due to niacin deficiency from serotonin overproduction) It often occurs with liver metastases, as the liver normally metabolizes serotonin before it reaches systemic circulation. Heart failure in carcinoid syndrome occurs due to carcinoid heart disease, where serotonin and other vasoactive substances cause fibrosis of the heart valves, primarily affecting the right-sided valves (tricuspid and pulmonary). This leads to tricuspid regurgitation, pulmonary stenosis, and eventually right heart failure. Liver metastases are the primary cause of carcinoid syndrome because they allow serotonin and vasoactive substances (e.g., histamine, bradykinin) to bypass first-pass 26metabolism by the liver and enter systemic circulation. 26 Pathological fracture Overview: • Fracturefrommild trauma dueto underlying bone weakness Causes: • Bonemetabolismdisorders →Osteoporosis, Paget’s disease, Osteomalacia • Bonetumours/metastases →Multiplemyeloma, Osteosarcoma, Prostate/Breast/Lung cancer mets Commonsites: spine, hip, wrist Classification: • Location, Malignant vs Benign, Completevs Incomplete 27 Pathological fracture Clinical features: Management: • Pain • Pain management – WHO • LimitedROM&functional impairment pain ladder • Nervecompressionsymptoms • Fracture stabilisation – • Systemic symptoms – weight loss, fever, immobilisation, surgery or night sweats other relevant Investigations: interventions • Labtests – Ca , K, PTH, ALP(for metabolic diseases) • Treat the underlying cause • Radiography – medical or surgical • CT/MRI/PET • Rehab and follow-up • Bonescans • Biopsy 28Pathological fractures 29 SBA 5 A65-year-oldmanwithahistory of lung cancer presents withfatigue, nausea, constipation, andpolyuria. He is alsomildly confused. Bloodtests show: • Calcium: 3.2 mmol/L (2.2–2.6) • PTH: 0.5 pmol/L (1.6–6.9) • ALP: 100 U/L (40–130) • Phosphate: 0.7 mmol/L (0.8–1.5) What is the most likelycause of his hypercalcaemia? A) Primaryhyperparathyroidism B) Familial hypocalciuric hypercalcaemia (FHH) C) Hypercalcaemia of malignancy D) VitaminDtoxicity E) Multiple myeloma Answer: C) Hypercalcaemia of malignancy •Low PTH with markedly elevated calcium suggests PTH-independent hypercalcaemia. •Common in lung cancers (especially squamous cell carcinoma) due to PTH-related peptide (PTHrP) secretion. •Other possible causes: osteolytic metastases or excess calcitriol from lymphoma. 30 SBA 6 A55-year-oldwomanpresents withepisodes of flushing, diarrhea, andwheezing. On examination, she has right-sidedheart murmurs. Echtumour?graphyshows tricuspidregurgitation. What is the most likelysite of the primary A. Lung B. Small intestine C. Pancreas D. Rectum E. Adrenal gland Answer: B) Small intestine •Classic carcinoid syndrome with flushing, diarrhea, right-sided valvular disease. •Small bowel (ileum) carcinoid tumors commonly metastasize to the liver, allowing serotonin to enter systemic circulation. 31 SESSION CONTENT ü Endo: ü Malignancy: ü Bones: ü Hyperparathyroidism ü Hypercalcaemia of ü Paget’s Disease (Primary, secondary, malignancy ü Osteoporosis tertiary) ü Metastatic disease ü Hypoparathyroidism (carcinoid syndrome) ü Pathological fracture ü Osteomalacia 32 Paget’s disease Overview: • Disorder of abnormal boneturnover →excessiveosteoclast resorption followed by disorganised osteoblast formation • Affects skull, spine, pelvis, femur, tibia • Incidence: 10 per 100,000 per year (only 5%symptomatic) • Morecommon in males (3:2), peaks 70+ years Risk Factors &Aetiology: • Age>40, Malesex, Family history • Genetic mutation (SQSTM1) →7-10x higher risk in 1 relatives • Environmental factors (possibleviral trigger, geographical variation) 33 Paget’s disease Signs &Symptoms: • Often asymptomatic • Bonepain(pelvis, lumbar spine, femur) • Bony deformities →bossedskull, bowedlegs • Nervecompression→hearing loss, visionchanges, carpal tunnel • High-output heart failure • Pathological fractures, osteoarthritis, kidney stones Investigations: • Bloods →↑ALP(normal calcium&phosphate) • X-ray →Osteolysis →mixedlytic/sclerotic lesions • Skull X-ray →Thickenedvault, osteoporosis circumscripta • BoneScintigraphy →Focal increaseduptake How does HF arise? In Paget’s disease, the bones develop extra blood vessels, which forces the heart to pump harder and faster to supply them. Over time, this extra workload wears out the heart, leading to heart failure. This is called high-output heart failure because the heart is pumping a lot, but it still can’t keep up with the demand. Bone scintigraphy, also known as a bone scan, is a diagnostic imaging technique that uses a small amount of radioactive material (called a radiotracer) to assess bone metabolism and detect abnormalities in the bones. •Thickened calvarium → Excessive bone formation leads to an enlarged, sclerotic skull. •Ill-defined lucent areas (osteolysis) → Early phase with increased bone resorption creates patchy bone loss. •Coarsening of trabeculae & increased bone density → Irregular new bone formation results in thickened but structurally weak bone. These changes reflect the mixed lytic and sclerotic phases of the disease. 34Sclerotic changes are disorganized and chaotic – making them brittle and weaker Skull showing thickening of the Calvarium – ill defined lucent areas Left Hemipelvic bones – increased density – coarsening of the trabeculae 34 Paget’s disease Management: • Bisphosphonates (1st line) →Alendronic acid(oral), Pamidronate/Zoledronic acid(IV) • Painrelief →Analgesics, NSAIDs • Physiotherapy, orthotics, surgical interventionif severe • Treat for 6months àMonitor ALPevery 6-12months to check for reoccurence Complications: • Pathological fractures, Osteoarthritis, Bonedeformity • Hearing loss (cranial nerveentrapment), Skull thickening • High-output heart failure • Osteosarcoma (1%if disease>10years) Alkaline phosphatase (ALP) is checked in Paget’s disease because it is a marker of bone turnover. In Paget’s, excessive bone breakdown and formation cause osteoblasts to work harder, leading to increased ALP levels. This helps in diagnosing the disease and monitoring treatment response. 35 Osteoporosis Overview: Clinical features: • Asymptomatic until fractures • Lowbonedensity &micro- &increasedfractureriskàbonefragility occur • fragility fractures • F>M(4:1), ageof onset: 50-70years. • Back pain– vertebral fracture • Primary: Postmenopausal (decreased Investigations: oestrogen), senileosteoporosis, • Bloods + Boneprofile(ALP, Ca, rheumatoidarthritis PTH, PO4) • Secondary: Drug-induced(steroids, PPIs, anticonvulsants, • DEXA: T-score≤-2.5= anticoagulants), hypogonadism, osteoporosis. hyperthyroidism, Cushing’s • X-Ray: For vertebral fractures. • Risk Factors: Smoking, low • FRAX: 10-year fracturerisk calcium/Vit D, lowbody weight. estimate. •DEXA → gold standard for measurement of bone density. T-score ≤-2.5 indicates osteoporosis. (Osteopenia = -1 to -2.5) • T-Score = bone density as a standard deviation compared to reference population of healthy young adults (ie. -2.5 = 2.5 SD’s below that of an average healthy young adult) • Z-Score = adjusts for age, gender and ethnicity 36 Osteoporosis Management • First-Line: Bisphosphonates (e.g., Alendronate) reduceboneresorption • Side effects: oesophagitis, osteonecrosis of the jaw. • Alternative: Risedronatefor GI side effects • Second-Line: Denosumabfor postmenopausal women • CalciumandVitaminDsupplementation • Teriparatide (PTHanalogue) • avoidance of glucocorticoids Complications: • Fractures: Commonsites: hip, wrist, rib Prognosis: • Preventive treatments helpavoidfragility fractures andmanage bone loss 37 SBA 7 A72-year-oldpostmenopausal womanpresents withsudden-onset lower back painafter liftinga heavybox. She has nohistoryof trauma. DEXAscanshows a T-score of -3.2. Blood tests show: • Calcium: Normal • Phosphate: Normal • ALP: Normal • PTH: Normal What is the most likelydiagnosis? A) Osteoporosis B) Osteomalacia C) Hyperparathyroidism D) Multiple myeloma E) Bone metastases Answer: A) Osteoporosis Explanation: •Normal blood tests + vertebral fracture + low DEXA score → Osteoporosis. •Osteomalacia would show high ALP and low calcium/phosphate. •Multiple myeloma would show high calcium and high total protein. 38 SBA 8 A70-year-oldmanpresents withworsening bone painandhearing loss. X-ray of the skull shows thickenedcortical bone withmixedlytic andsclerotic changes. Bloodtests show: • Calcium: Normal • Phosphate: Normal • ALP: 780U/L (High) • PTH: Normal What is the most appropriate first-line treatment? A) Denosumab B) Conservative management withpainrelief C) Alendronic acid D) CalciumandVit Dsupplementation E) Calcitonin Answer: C) Alendronic acid 39 SESSION CONTENT ü Endo: ü Malignancy: ü Bones: ü Hyperparathyroidism ü Hypercalcaemia of ü Paget’s Disease (Primary, secondary, malignancy ü Osteoporosis tertiary) ü Metastatic disease ü Hypoparathyroidism (carcinoid syndrome) ü Pathological fracture ü Osteomalacia 40THANK YOU. qm420@ic.ac.uk 41