Week 1: Arthritis
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Questions and Answers

What is a common characteristic of pain due to pressure on nerves?

  • Dull and persistent
  • Burning and radiating
  • Numbness and tingling (correct)
  • Throbbing and pulsating

    • How is pain of non-inflammatory origin typically related to activity?

  • It improves with increased activity
  • The less you do, the worse it gets
  • It remains constant regardless of activity level
  • The more you do, the worse it gets (correct)

    • What type of pain is often present at rest as well as on use, and tends to vary unpredictably?

  • Bone-related pain
  • Nerve-related pain
  • Muscle-related pain
  • Pain caused by inflammation (correct)

    • Which type of arthritis is associated with prolonged morning stiffness that may last for several hours?

    <p>Inflammatory arthritis</p> Signup and view all the answers

    What can joint swelling, especially if intermittent, indicate?

    <p>An inflammatory disease process</p> Signup and view all the answers

    What type of arthritis tends to cause localised stiffness that may be short-lasting but can recur after sitting for short periods?

    <p>Osteoarthritis</p> Signup and view all the answers

    What is a common complaint associated with ankle swelling?

    <p>Oedema rather than joint swelling</p> Signup and view all the answers

    What type of pain is severe bone pain often suggestive of?

    <p>Underlying malignancy</p> Signup and view all the answers

    What does intermittent joint swelling sometimes feel like according to patients?

    <p>Rings becoming tight or walking on pebbles</p> Signup and view all the answers

    What type of pain tends to be relieved by rest?

    <p>Inflammatory pain</p> Signup and view all the answers

    Which symptom is more associated with inflammatory joint conditions like rheumatoid arthritis (RA)?

    <p>Prolonged early morning stiffness</p> Signup and view all the answers

    What distinguishes non-inflammatory conditions like osteoarthritis (OA) from inflammatory joint conditions?

    <p>Pain more than stiffness</p> Signup and view all the answers

    In the shoulder, where is pain from the acromioclavicular joint usually felt?

    <p>In that joint</p> Signup and view all the answers

    Where is pain from the glenohumeral joint or rotator cuff usually felt in the shoulder?

    <p>In the upper arm</p> Signup and view all the answers

    What type of pain is associated with tennis elbow?

    <p>On the outside of the elbow joint</p> Signup and view all the answers

    What does it mean if a patient localizes their pain accurately to the affected joint?

    <p>The pain is likely due to inflammation</p> Signup and view all the answers

    What distinguishes inflammatory and non-inflammatory musculoskeletal conditions based on symptoms?

    <p>Character of pain</p> Signup and view all the answers

    Where might pain from the knee be felt, other than in the knee itself?

    <p>Hip or ankle</p> Signup and view all the answers

    What type of pain is associated with irritation of a nerve, such as in sciatica?

    <p>Sharp and stabbing</p> Signup and view all the answers

    What distinguishes pain from inflammatory joint conditions like rheumatoid arthritis (RA) from non-inflammatory conditions like osteoarthritis (OA)?

    <p>Presence of prolonged early morning stiffness</p> Signup and view all the answers

    Where might pain due to irritation of a nerve be felt?

    <p>In the distribution of the nerve</p> Signup and view all the answers

    Which of the following is a key feature of psoriatic arthritis?

    <p>Presence of salmon pink plaques on extensor surfaces</p> Signup and view all the answers

    What is a common feature of several rheumatological diseases?

    <p>Fatigue, malaise, and weight loss</p> Signup and view all the answers

    What is a key component of history taking in exploring a patient's concerns and expectations?

    <p>Exploration of ICE (ideas, concerns, expectations)</p> Signup and view all the answers

    What does signposting involve in a history taking context?

    <p>Explicitly stating what has been discussed and what will be discussed next</p> Signup and view all the answers

    What should be assessed when asking about medical conditions?

    <p>Complications associated with the condition including hospital admissions</p> Signup and view all the answers

    'Intravenous drug use is a risk factor for which condition?'

    <p>Septic arthritis</p> Signup and view all the answers

    'When should joint swelling and fever prompt urgent review and investigation?'

    <p>When associated with a systemic illness or significant systemic upset</p> Signup and view all the answers

    What is an effective approach to history taking at the start of consultations?

    <p>Using open questions to allow the patient to explain their symptoms</p> Signup and view all the answers

    What is the purpose of closed questions in history taking?

    <p>To explore symptoms in more detail and gain a better understanding of the presentation</p> Signup and view all the answers

    Why is it important to demonstrate general communication skills during history taking?

    <p>To ensure the consultation remains patient-centered</p> Signup and view all the answers

    What is an important initial step before proceeding with history taking in an OSCE setting?

    <p>Washing hands and donning appropriate PPE if necessary</p> Signup and view all the answers

    How does using open questions contribute to effective history taking?

    <p>Allows the patient to tell you what has happened in their own words</p> Signup and view all the answers

    Why is it important not to forget general communication skills during history taking?

    <p>To ensure your consultation remains patient-centered and not checklist-like</p> Signup and view all the answers

    What does gaining consent before proceeding with history taking indicate?

    <p>Respect for patient autonomy and decision-making</p> Signup and view all the answers

    Why should closed questions be used during history taking?

    <p>To explore symptoms mentioned by the patient in more detail and gain a better understanding of their presentation.</p> Signup and view all the answers

    What should be done before proceeding with history taking?

    <p>Wash your hands and don PPE if appropriate.</p> Signup and view all the answers

    Why is it important to facilitate patients to expand on their presenting complaint if required?

    <p>History taking typically involves a combination of open and closed questions.</p> Signup and view all the answers

    What is the process of skeletal change known as?

    <p>Bone remodeling</p> Signup and view all the answers

    Who developed the law that describes the nature of bone remodeling regarding stresses?

    <p>Julius Wolff</p> Signup and view all the answers

    Which cells are responsible for the resorption and deposition phases of bone remodeling?

    <p>Osteoblasts and osteoclasts</p> Signup and view all the answers

    What dictates how the integrity of the bone is altered in response to forces applied?

    <p>Duration, magnitude, and rate of forces applied to the bone</p> Signup and view all the answers

    Which cells are influenced directly or indirectly by hormonal signals in bone remodeling?

    <p>Osteoblasts and osteoclasts</p> Signup and view all the answers

    What did Julius Wolff's law state about bones adapting to mechanical loading?

    <p>An increase in loading causes strengthening of internal, spongy bone followed by the cortical layer</p> Signup and view all the answers

    What contributes metabolically to the body's balance of calcium and phosphorus?

    <p>Bone remodeling</p> Signup and view all the answers

    Which marker is specific to bone formation?

    <p>Osteocalcin (OC)</p> Signup and view all the answers

    What is the primary cause of osteoporosis?

    <p>Decrease in estrogen</p> Signup and view all the answers

    Which condition is characterized by abnormal bone resorption and irregular osteoblastic response?

    <p>Paget disease</p> Signup and view all the answers

    What is the function of bisphosphonates in treating osteoporosis?

    <p>Inhibit osteoclast attachment to bone surface and bone resorption</p> Signup and view all the answers

    What is the characteristic feature of osteopetrosis?

    <p>Increased bone mass and weak bone integrity</p> Signup and view all the answers

    What imaging technique is used for bone scintigraphy?

    <p>Nuclear medicine with a gamma camera and technetium-99m-MDP injection</p> Signup and view all the answers

    What does dual-energy X-ray absorptiometry (DEXA) measure?

    <p>Bone mineral content and diagnose osteoporosis</p> Signup and view all the answers

    Which medication inhibits osteoclast activity and increases the renal excretion of calcium?

    <p>Calcitonin</p> Signup and view all the answers

    What is the mechanism of action of Denosumab?

    <p>Binds RANKL</p> Signup and view all the answers

    Which medication has agonist activity in bone and antagonist activity in other tissues?

    <p>Raloxifene</p> Signup and view all the answers

    Why are non-nitrogen-containing bisphosphonates no longer typically prescribed?

    <p>They inhibit bone mineralization</p> Signup and view all the answers

    What is the primary effect of Raloxifene in bone?

    <p>Decreases osteoclast survival</p> Signup and view all the answers

    Which medication decreases the activity and survival of osteoclasts by inhibiting the RANK-RANKL interaction?

    <p>Denosumab</p> Signup and view all the answers

    What cell lineage do osteoblasts and osteoclasts derive from?

    <p>Mesenchymal stem cells and hematopoietic lineage in bone marrow</p> Signup and view all the answers

    What is the role of osteocytes in bone remodeling?

    <p>Transmitting signals regarding bone stress and regulating fluid flow</p> Signup and view all the answers

    Which hormone acts to increase calcium levels in the bloodstream?

    <p>Parathyroid Hormone (PTH)</p> Signup and view all the answers

    What effect do glucocorticoids have on bone formation?

    <p>Decrease bone formation and cause osteoblast cell death</p> Signup and view all the answers

    What is the consequence of estrogen deficiency on bone remodeling?

    <p>Increased bone remodeling and decreased bone mass</p> Signup and view all the answers

    What is the function of Calcitonin in bone remodeling?

    <p>Inhibit bone resorption</p> Signup and view all the answers

    Which type of joint is typically lined with hyaline cartilage and has a wedge of fibrocartilage joining the bones?

    <p>Cartilaginous joint</p> Signup and view all the answers

    What contributes to joint stability?

    <p>Nature of the articulation, ligaments, and muscle tone</p> Signup and view all the answers

    Which joint type permits the greatest movement?

    <p>Synovial joint</p> Signup and view all the answers

    What is an example of a fibrous joint?

    <p>Sutures joining the bones of the skull</p> Signup and view all the answers

    What is the primary gender demographic affected by rheumatoid arthritis (RA)?

    <p>Females</p> Signup and view all the answers

    What is the key improvement index for desirable outcomes in RA?

    <p>Early diagnosis</p> Signup and view all the answers

    What is the optimal therapeutic window for early symptoms of RA?

    <p>12 weeks</p> Signup and view all the answers

    What are the clinical manifestations of symmetrical joint involvement in RA?

    <p>Swelling, redness, and limited range of motion</p> Signup and view all the answers

    Which cytokines involved in RA can promote osteoclastogenesis and suppress bone formation?

    <p>TNF-α and IL-6</p> Signup and view all the answers

    What is the cornerstone in RA treatment, acting through various mechanisms including folate antagonism and downregulation of adhesion molecules?

    <p>Methotrexate (MTX)</p> Signup and view all the answers

    What might contribute to bone loss in RA by targeting osteoclasts?

    <p>Formation of anti-citrullinated vimentin antibodies</p> Signup and view all the answers

    What is a known side effect of Methotrexate (MTX) interaction with other drugs?

    <p>Hepatotoxic effects</p> Signup and view all the answers

    Which organs are affected by RA, leading to sarcopenia among other conditions?

    <p>Skeletal muscles</p> Signup and view all the answers

    What is a potential consequence of destruction of subchondral bone in weight-bearing joints?

    <p>Articular cartilage degeneration</p> Signup and view all the answers

    Which cells are activated in the articular joints due to early cartilage damage in RA?

    <p>Fibroblast-like synoviocytes (FLS)</p> Signup and view all the answers

    What is a potential effect of cytokines involved in RA on cardiovascular health?

    <p>Promoting endothelial activation leading to unstable atheromatous plaques</p> Signup and view all the answers

    What is the primary mechanism through which Methotrexate (MTX) acts as a cornerstone in RA treatment?

    <p>Folate antagonism and downregulation of adhesion molecules</p> Signup and view all the answers

    Which autoimmune mechanisms may contribute to bone loss in RA?

    <p>Formation of immune complexes and Fc-receptor-mediated osteoclast differentiation, and formation of anti-citrullinated vimentin antibodies targeting osteoclasts.</p> Signup and view all the answers

    What is the route of administration for Methotrexate (MTX) in RA treatment?

    <p>Low-dose weekly regimen with oral or subcutaneous administration</p> Signup and view all the answers

    Which scale is used for measuring disease activity in rheumatoid arthritis?

    <p>DAS-28</p> Signup and view all the answers

    What is the primary aim of treatment for rheumatoid arthritis?

    <p>Achieve a low disease activity state (LDAS)</p> Signup and view all the answers

    Which genetic factors are major risk factors for rheumatoid arthritis?

    <p>HLA-DR1 and HLA-DR4</p> Signup and view all the answers

    What may trigger ACPA production in rheumatoid arthritis?

    <p>Lung exposure to noxious agents and ER-Golgi transport disruptions</p> Signup and view all the answers

    What has gained attention in recent years due to its effectiveness in attenuating disease activity in rheumatoid arthritis?

    <p>DMARDs</p> Signup and view all the answers

    What type of drugs are available for rheumatoid arthritis treatment?

    <p>Traditional synthetic drugs, biological DMARDs, and novel potential small molecules</p> Signup and view all the answers

    What is the routine starting dose of Leflunomide for the initial 3 days?

    <p>10 mg daily</p> Signup and view all the answers

    Which adverse effect is commonly associated with Sulfasalazine?

    <p>Hair loss</p> Signup and view all the answers

    What is the primary mechanism of action of Hydroxychloroquine in reducing joint inflammation in RA patients?

    <p>Interference with T helper cell and macrophage interaction</p> Signup and view all the answers

    What do biological DMARDs (bDMARDs) target in the treatment of RA?

    <p>Specific molecules or molecular pathways involved in RA inflammatory processes</p> Signup and view all the answers

    What is the proposed role of TNF-α in mediating local bone destruction in inflammatory musculoskeletal diseases?

    <p>Induction of metalloproteinases and adhesion molecules</p> Signup and view all the answers

    What is the primary adverse effect associated with Leflunomide that may require dose reduction?

    <p>Liver failure</p> Signup and view all the answers

    What is the potential risk associated with long duration and high dose use of Hydroxychloroquine?

    <p>Ophthalmologic toxicity</p> Signup and view all the answers

    What are the metabolites of Sulfasalazine?

    <p>Sulfapyridine and 5-aminosalicylic acid (5-ASA)</p> Signup and view all the answers

    What is the primary role of TNF-α in inflammatory musculoskeletal diseases?

    <p>Induction of metalloproteinases and adhesion molecules</p> Signup and view all the answers

    Which infectious agent is associated with higher rates in RA patients, leading to neutrophil hyper citrullination and release of citrullinated autoantigens in the gums?

    <p>Aggregatibacter actinomycetemcomitans (Aa)</p> Signup and view all the answers

    Which factor has been shown to lower the risk of ACPA production and prevent RA onset?

    <p>Omega-3 fatty acids</p> Signup and view all the answers

    What is the primary cause of cartilage damage in RA?

    <p>Directed adhesion and invasion</p> Signup and view all the answers

    Which infectious agent can affect ACPA-producing B cells and impaired EBV control is observed in RA?

    <p>Epstein-Barr virus (EBV)</p> Signup and view all the answers

    What plays a role in smoking and genotype interaction in ANPA-positive RA?

    <p>DNA methylation</p> Signup and view all the answers

    What is linked to RA through their ability to trigger autoimmune responses and contribute to citrullinated autoantigens production?

    <p>P. gingivalis, Aa, and EBV</p> Signup and view all the answers

    What has been implicated in RA pathology, but the association with ACPA is not well established?

    <p>Hormonal levels</p> Signup and view all the answers

    What leads to hyperplastic synovium, which produces inflammatory cytokines and proteinases that perpetuate joint destruction in RA?

    <p>Loss of contact inhibition in FLS</p> Signup and view all the answers

    What causes major cartilage damage by degrading type II collagen and glycosaminoglycans?

    <p>Membrane-type I MMP</p> Signup and view all the answers

    What contributes to joint destruction in RA by targeting osteoclasts?

    <p>Inflammatory cytokines</p> Signup and view all the answers

    Which type of psoriatic arthritis primarily affects the DIP joints?

    <p>Distal interphalangeal predominant pattern</p> Signup and view all the answers

    What is the most common form of psoriatic arthritis that presents similarly to rheumatoid arthritis?

    <p>Symmetrical polyarthritis</p> Signup and view all the answers

    Which form of psoriatic arthritis involves back stiffness and pain, primarily affecting the axial skeleton?

    <p>Spondylitis</p> Signup and view all the answers

    What is the most severe form of psoriatic arthritis that affects the phalanges (the bones of the fingers and toes)?

    <p>Arthritis mutilans</p> Signup and view all the answers

    Which characteristic x-ray finding is associated with arthritis mutilans in psoriatic arthritis?

    <p>Pencil-in-cup appearance</p> Signup and view all the answers

    What is the Psoriasis Epidemiological Screening Tool (PEST) used for?

    <p>Screening for psoriatic arthritis in patients with psoriasis</p> Signup and view all the answers

    Which joints does psoriatic arthritis tend to affect, distinguishing it from rheumatoid arthritis?

    <p>Distal interphalangeal (DIP) joints and axial skeleton</p> Signup and view all the answers

    What is the recommended approach for managing psoriatic arthritis?

    <p>Coordinated treatment between dermatologists, rheumatologists, and multidisciplinary team members</p> Signup and view all the answers

    What is the most commonly affected joint in gout?

    <p>Big toe (first metatarsophalangeal joint)</p> Signup and view all the answers

    What is the characteristic appearance of monosodium urate crystals under polarised light?

    <p>Needle-shaped and negatively birefringent</p> Signup and view all the answers

    What is the critical differential diagnosis for gout presentation?

    <p>Septic arthritis</p> Signup and view all the answers

    Where are gouty tophi typically seen?

    <p>Hands, elbows, and ears</p> Signup and view all the answers

    What is the management for acute flares of gout?

    <p>Colchicine</p> Signup and view all the answers

    What is the primary prophylactic treatment for gout after an acute attack has resolved?

    <p>Xanthine oxidase inhibitors</p> Signup and view all the answers

    What lifestyle changes can help reduce the risk of gout?

    <p>Losing weight and staying hydrated</p> Signup and view all the answers

    When should prophylaxis for gout be initiated?

    <p>Weeks after the acute attack has resolved</p> Signup and view all the answers

    What is the recommended duration for continuing antibiotics in the treatment of joint infections?

    <p>4-6 weeks</p> Signup and view all the answers

    What is the purpose of joint aspiration before starting antibiotics in the treatment of joint infections?

    <p>To determine the type of organism causing the infection</p> Signup and view all the answers

    What is the recommended initial route of administration for antibiotics in the treatment of joint infections?

    <p>Intravenous administration</p> Signup and view all the answers

    What is the mortality rate associated with septic arthritis?

    <p>10%</p> Signup and view all the answers

    In which type of surgery is infection more likely to occur?

    <p>Revision surgery</p> Signup and view all the answers

    Which bacterium is the most common causative organism for septic arthritis?

    <p>Staphylococcus aureus</p> Signup and view all the answers

    What should be considered in a young patient presenting with a single acutely swollen joint until proven otherwise?

    <p>Reactive arthritis</p> Signup and view all the answers

    What is the main factor governing the type of bone healing achieved at the fracture site?

    <p>The mechanical stability at the fracture site and the consequent strain</p> Signup and view all the answers

    What is the primary difference between primary and secondary bone healing?

    <p>Primary bone healing occurs through intramembranous bone healing, while secondary bone healing occurs via endochondral bone healing</p> Signup and view all the answers

    What kind of mechanical strain achieves primary bone healing?

    <p>Below 2%</p> Signup and view all the answers

    Which fixation modality achieves a mechanical strain between 2-10% for secondary bone healing?

    <p>External fixation</p> Signup and view all the answers

    What is the process by which mesenchymal tissue is converted directly to bone, with no cartilage intermediate?

    <p>Intramembranous ossification</p> Signup and view all the answers

    What is the name given for the process of conversion of cartilage to bone?

    <p>Endochondral ossification</p> Signup and view all the answers

    What stimulates bone formation on the compression side and osteoclasts on the tension side?

    <p>Wolff's law</p> Signup and view all the answers

    What inhibits the activation of osteoclast precursor cells by occupying the binding site of RANK?

    <p>Osteoprotegerin (OPG)</p> Signup and view all the answers

    What results in osteoclasts differentiation and activation by interacting with RANK expressed by osteoclasts?

    <p>RANKL</p> Signup and view all the answers

    What occurs at the junction of maturing chondrocytes and newly forming bone?

    <p>Apoptosis of chondrocytes</p> Signup and view all the answers

    Which type of bone ultimately replaces the center of the callus during coupled remodeling?

    <p>Compact bone</p> Signup and view all the answers

    What occurs during forming a bony callus when newly formed collagen-rich cartilaginous callus gets replaced by immature bone?

    <p>Endochondral ossification</p> Signup and view all the answers

    What is the primary bone healing phase where stem cells are recruited and differentiated, leading to cartilaginous callus formation and primary bone formation?

    <p>Anabolic phase</p> Signup and view all the answers

    Which phase of fracture healing provides provisional stability, triggers an inflammatory response, and initiates fibrocartilaginous callus formation?

    <p>Callus formation</p> Signup and view all the answers

    What is the crucial step in fracture healing where disrupted blood vessels cause clotting and provide a temporary frame for subsequent healing?

    <p>Hematoma formation</p> Signup and view all the answers

    Which cells are involved in concurrent angiogenesis during fracture healing, resulting in the mineralization of the extracellular matrix and chondrocyte apoptosis?

    <p>MSCs (mesenchymal stem cells)</p> Signup and view all the answers

    What phase of bone fracture healing involves the interaction of signaling pathways to differentiate the appendicular skeleton for months to years after clinical union?

    <p>Bone remodeling</p> Signup and view all the answers

    What is the mechanical strain percentage range for secondary bone healing?

    <p>2-10%</p> Signup and view all the answers

    Which type of bone healing is characterized by mechanical strain greater than 10%?

    <p>Tertiary bone healing</p> Signup and view all the answers

    What is the primary purpose of granulation tissue formation during fracture healing?

    <p>Provisional stability</p> Signup and view all the answers

    Which cells are involved in laying down woven bone and calcifying the cartilaginous callus during fracture healing?

    <p>Osteoblasts</p> Signup and view all the answers

    What continues for months to years after clinical union, involving the interaction of signaling pathways to differentiate the appendicular skeleton?

    <p>Bone remodeling</p> Signup and view all the answers

    What occurs concurrently with anabolic phase during fracture healing, resulting in mineralization of extracellular matrix and chondrocyte apoptosis?

    <p>Angiogenesis</p> Signup and view all the answers

    Which medication is a selective estrogen receptor modulator combined with conjugated estrogen approved by the FDA for osteoporosis prevention but not for treatment?

    <p>Raloxifene</p> Signup and view all the answers

    What is the primary function of teriparatide in osteoporosis treatment?

    <p>Stimulate osteoblasts to produce more bone</p> Signup and view all the answers

    Which medication inhibits farnesyl pyrophosphate synthase, leading to inhibition of osteoclast resorption and induction of osteocyte apoptosis?

    <p>Zoledronic acid</p> Signup and view all the answers

    What is the mechanism of action of denosumab in treating osteoporosis?

    <p>Inhibit osteoclast activation by targeting RANKL</p> Signup and view all the answers

    What is the recommended first-line therapy for men with osteoporosis?

    <p>Alendronate</p> Signup and view all the answers

    What is the most common cause of nutritional rickets?

    <p>Vitamin D deficiency</p> Signup and view all the answers

    Which medication can impair vitamin D metabolism and result in rickets?

    <p>Diphenylhydantoin</p> Signup and view all the answers

    What type of rickets may result from poor calcium absorption in children with malabsorption syndromes?

    <p>Calcipenic rickets</p> Signup and view all the answers

    What stimulates the secretion of parathyroid hormone (PTH) in calcipenic rickets?

    <p>Low serum calcium levels</p> Signup and view all the answers

    What is the recommended daily vitamin D supplementation for pregnant women to prevent rickets in their offsprings?

    <p>600 IU</p> Signup and view all the answers

    What is the recommended daily oral vitamin D supplementation for breastfed infants and infants who consume less than 500 mL of fortified formula per day in the first year of their life?

    <p>400 IU</p> Signup and view all the answers

    What is the recommended daily vitamin D supplementation for high-risk groups for vitamin D deficiency beyond infancy?

    <p>$600 IU$</p> Signup and view all the answers

    What is the treatment for vitamin D-dependent rickets type I A (VDDR1A) and vitamin D-dependent rickets type I B (VDDR1B)?

    <p>$1,25-dihydroxyvitamin D$</p> Signup and view all the answers

    What is the treatment for vitamin D-dependent rickets type II A (VDDR2A) and vitamin D-dependent rickets type II B (VDDR2B)?

    <p>$High doses of calcitriol and calcium$</p> Signup and view all the answers

    What is the long term management for familial hypophosphatemic rickets?

    Signup and view all the answers

    What was the effect of a nationwide program in Turkey that introduced free vitamin D drops (400 IU/day) to children less than three years?

    <p>Decreased prevalence of rickets from 6% to 0.1%</p> Signup and view all the answers

    What was the recommendation for residents located higher than 55th attitudes in Canada regarding daily maintenance doses of Vitamin D?

    <p>800 IU through dietary sources and/or vitamin D supplementation.</p> Signup and view all the answers

    Which serum 25-hydroxyvitamin D level is defined as insufficiency?

    <p>30 to 50 ng/mL</p> Signup and view all the answers

    What is the recommended dose of vitamin D for infants in single-dose therapy (stoss therapy)?

    <p>5000 IU</p> Signup and view all the answers

    What is the recommended daily dose of vitamin D for children aged 1-12 months in multiple doses therapy?

    <p>2000 IU</p> Signup and view all the answers

    Which biochemical abnormality may persist longer after the initiation of rickets treatment?

    <p>$ALP$ levels</p> Signup and view all the answers

    In which type of rickets are serum calcium and PTH levels usually normal?

    <p>$Phosphopenic$ rickets</p> Signup and view all the answers

    What radiological change is the earliest sign of rickets?

    <p>$Widening$ of epiphyseal plate</p> Signup and view all the answers

    Bone pain improves within two weeks after treatment initiation refers to which age group?

    <p>$Toddlers$</p> Signup and view all the answers

    What is the primary cause of rickets?

    <p>Defects in the osteoid mineralization process</p> Signup and view all the answers

    What is the most common reason for limited sun exposure leading to vitamin D deficiency?

    <p>Clothing and indoor living</p> Signup and view all the answers

    Which region has the highest prevalence of rickets?

    <p>Africa</p> Signup and view all the answers

    What is necessary for normal mineralization in the context of rickets?

    <p>$\text{Vitamin D}$</p> Signup and view all the answers

    Which factor contributes to the high incidence of rickets in Alaska?

    <p>$\text{Higher latitudes and lowest sunlight}$</p> Signup and view all the answers

    What leads to hypophosphatemia and accumulation of hypertrophic chondrocytes in rickets?

    <p>$\text{Low serum phosphate levels}$</p> Signup and view all the answers

    What does evaluation for rickets typically include?

    <p>$\text{Serum alkaline phosphatase (ALP)}$ and $\text{serum 25-hydroxyvitamin D level}$</p> Signup and view all the answers

    What is a contributing factor to decreased prevalence of rickets in developed countries?

    <p>$\text{Improved air quality}$ and $\text{public awareness}$</p> Signup and view all the answers

    What are the primary sources of vitamin D for normal mineralization in rickets?

    <p>$\text{Diet or UVB exposure}$</p> Signup and view all the answers

    Which of the following is a characteristic of FGF-23-independent hypophosphatemic rickets?

    <p>Pathology in the renal tubules causing phosphate transport defects</p> Signup and view all the answers

    What is the main cause of rickets worldwide in older infants and toddlers?

    <p>Vitamin D deficiency</p> Signup and view all the answers

    What can predispose babies to rickets and hypocalcemia?

    <p>Vitamin D deficiency in pregnant mothers</p> Signup and view all the answers

    What type of rickets is characterized by defects in vitamin D synthesis, vitamin D receptor, or vitamin D-VDR interactions?

    <p>Vitamin D-dependent rickets (VDDR)</p> Signup and view all the answers

    What is a risk factor for nutritional vitamin D deficiency?

    <p>Improper function</p> Signup and view all the answers

    What can lead to internalization of phosphate co-transporters in renal tubules?

    <p>Secondary hyperparathyroidism</p> Signup and view all the answers

    What characterizes calcipenic rickets and phosphopenic rickets?

    <p>Hypophosphatemia and rachitic bone changes</p> Signup and view all the answers

    What causes inhibited mineralization rickets?

    <p>Inhibition of mineralization due to defects in growth plate mineralization with normal calcium and phosphate levels</p> Signup and view all the answers

    What leads to increased renal phosphate loss?

    <p>Inactivation of sodium-dependent phosphate transporters in the kidneys</p> Signup and view all the answers

    What is the main cause of fibroblast growth factor 23 (FGF23)?

    <p>Increases renal phosphate loss and decreases reabsorption.</p> Signup and view all the answers

    What type of mutations cause end-organ resistance to the active form of vitamin D?

    <p>Mutations leading to end-organ resistance to the active form of vitamin D</p> Signup and view all the answers

    What is the recommended analgesic for mild pain?

    <p>Mild opioids like codeine</p> Signup and view all the answers

    What type of pain are NSAIDs particularly effective for?

    <p>Pain of musculoskeletal origin such as arthritis</p> Signup and view all the answers

    For which conditions should strong opioids like morphine be reserved?

    <p>Operations, labour, and cancer pain</p> Signup and view all the answers

    Which type of pain is mild opioids such as codeine beneficial for?

    <p>Severe pain</p> Signup and view all the answers

    For what conditions should strong opioids such as morphine, fentanyl, and pethidine be reserved?

    <p>Operations, labour, and cancer pain</p> Signup and view all the answers

    What is a more suitable alternative pain management technique for pain of neuropathic origin or of a longer duration?

    <p>Local anaesthetic injections and tricyclics</p> Signup and view all the answers

    What is the primary role of calcitonin in calcium homeostasis?

    <p>Decreasing calcium levels by inhibiting osteoclasts</p> Signup and view all the answers

    Which condition is NOT a symptom of hypercalcemia?

    <p>Excessive thirst and urination</p> Signup and view all the answers

    What is a potential cause of hypercalcemia?

    <p>Excess vitamin D causing increased intestinal absorption of calcium</p> Signup and view all the answers

    Which medication can contribute to hypercalcemia by increasing renal reabsorption of calcium?

    <p>Thiazide diuretics</p> Signup and view all the answers

    Which hormone is secreted by the thyroid glands to regulate the amount of calcium in the blood?

    <p>Calcitriol</p> Signup and view all the answers

    What is the main function of calcitriol (vitamin D) in relation to calcium?

    <p>Increase intestinal absorption of calcium</p> Signup and view all the answers

    What happens when levels of calcitriol become excessive?

    <p>It is converted to 24,25-dihydroxycholecalciferol</p> Signup and view all the answers

    What stimulates chief cells in the parathyroid gland to secrete additional parathyroid hormone (PTH)?

    <p>Reduction in blood calcium levels</p> Signup and view all the answers

    What is the main function of calcitriol (vitamin D) in regulating serum calcium?

    <p>Stimulating intestinal epithelial cells to increase the synthesis of calbindin-D proteins</p> Signup and view all the answers

    How does parathyroid hormone (PTH) raise blood calcium levels?

    <p>By promoting the release of calcium into the bloodstream</p> Signup and view all the answers

    What is the consequence of excessive levels of calcitriol (vitamin D)?

    <p>Conversion to a less active form</p> Signup and view all the answers

    Where is calcitonin secreted from?

    <p>Thyroid glands</p> Signup and view all the answers

    What is the role of calcitonin in calcium homeostasis?

    <p>Decreases calcium levels by inhibiting osteoclasts</p> Signup and view all the answers

    What are the symptoms of hypercalcemia when levels exceed 3mmol/L?

    <p>Muscle weakness, cardiac arrhythmias, constipation, and kidney stones</p> Signup and view all the answers

    What can cause hypercalcaemia?

    <p>Malignant tumor secreting PTHrP</p> Signup and view all the answers

    How do thiazide diuretics contribute to hypercalcaemia?

    <p>By increasing renal reabsorption of calcium</p> Signup and view all the answers

    Study Notes

    • Bone remodeling begins in fetal life and involves two cell lineages: osteoblasts and osteoclasts.

    • Osteoblasts derive from mesenchymal stem cells and contribute to bone growth.

    • Osteoclasts originate from hematopoietic lineage in bone marrow and cause bone resorption.

    • Fusion of osteoblast and osteoclast precursors forms multinucleated osteoclast, which attaches to bone surface and commences resorption by breaking down bone matrix (hydroxyapatite and organic material).

    • Mononuclear macrophage lineage cells may conduct a "reversal" phase, depositing organic material and releasing growth factors to initiate bone deposition.

    • Differentiation of mesenchymal precursors fills "Howship lacunae" with new collagen and minerals.

    • Osteocytes, the most abundant cell type in mature bone, are situated in bone matrix and play a role in bone remodeling by transmitting signals regarding bone stress and regulating fluid flow.

    • Parathyroid Hormone (PTH) is a polypeptide hormone secreted by parathyroid glands and acts to increase calcium levels in bloodstream by influencing bone and kidney and indirectly acting on intestines via vitamin D.

    • Estrogen deficiency leads to increased bone remodeling and decreased bone mass, potentially due to blocking production and action of interleukin-6 and osteoclast survival thriving in its deficiency.

    • Calcitonin is a polypeptide hormone released from thyroid C cells in response to high calcium levels and inhibits bone resorption.

    • Growth Hormone (GH) is a peptide hormone secreted by pituitary gland and acts directly and indirectly through insulin-like growth factors to stimulate bone formation and resorption.

    • Glucocorticoids decrease bone formation and cause osteoblast cell death, favoring osteoclast survival.

    • Hormones such as Thyroid-stimulating hormone (TSH), thyroxine (T4), and triiodothyronine (T3) stimulate bone growth and elongation at epiphyseal plates.

    • Hypothyroidism and hyperthyroidism result in low and high rates of bone turnover, respectively, due to effect on number and activity level of osteoblasts and osteoclasts.

    • RA treatment outcomes and disease progression depend on patient awareness, timely diagnosis, and physician capability.

    • Poorly controlled or severe RA may lead to extra-articular manifestations such as keratitis, pulmonary granulomas, pericarditis/pleuritis, small vessel vasculitis, and other non-specific symptoms.

    • There is no cure for RA and treatment aims to achieve a low disease activity state (LDAS).

    • Composite scales for measuring disease activity include DAS-28, SDAI, and CDAI.

    • NSAIDs and corticosteroids are often used to relieve stiffness and pain but do not prevent disease progression.

    • DMARDs have gained attention in recent years due to their effectiveness in attenuating disease activity and delaying joint deformity.

    • Traditional synthetic drugs, biological DMARDs, and novel potential small molecules are available for RA treatment.

    • HLA-DR, especially HLA-DR1 and HLA-DR4, and PTPN22 are major genetic risk factors for RA. ACPA production is associated with these genes and with environmental factors.

    • ACPA can be detected before joint symptoms and may be triggered by lung exposure to noxious agents and ER-Golgi transport disruptions.

    • The role of the environment in gene-environment interaction and its impact on ACPA production is an ongoing area of research.

    • Genetic and environmental factors influence RA susceptibility and outcomes differently in men and women.

    • Familial factors and twin studies suggest that the risk of developing RA is increased in first-degree relatives of RA patients.

    • The environment plays a significant role in ACPA production and may act as a triggering factor in RA development.

    • Mutations in the coatomer subunit α gene can disrupt ER-Golgi transport and lead to hereditary autoimmune-mediated lung disease and arthritis.

    • Smoking and the HLA-DR SE gene interaction can cause immune reactions to citrullinated proteins in RA.

    • DNA methylation plays a role in smoking and genotype interaction in ANPA-positive RA.

    • Three infectious agents, Porphyromonas gingivalis (P. gingivalis), Aggregatibacter actinomycetemcomitans (Aa), and Epstein-Barr virus (EBV), are linked to RA through their ability to trigger autoimmune responses and contribute to citrullinated autoantigens production.

    • Aa infection is associated with higher rates in RA patients, leading to neutrophil hyper citrullination and release of citrullinated autoantigens in the gums.

    • P. gingivalis and ACPAs can promote each other's production through different mechanisms: PAD and Rgps of P. gingivalis, and NETosis induced by ACPAs.

    • EBV can affect ACPA-producing B cells and impaired EBV control is observed in RA.

    • Dysbiosis in RA patients, particularly in the intestinal tract, is linked to the pathogenesis of RA through multiple molecular mechanisms.

    • Omega-3 fatty acids have been shown to lower the risk of ACPA production and prevent RA onset.

    • Hormonal levels have been implicated in RA pathology, but the association with ACPA is not well established.

    • The loss of contact inhibition in FLS leads to hyperplastic synovium, which produces inflammatory cytokines and proteinases, such as MMPs and TIMPs, that perpetuate joint destruction in RA.

    • Hyperplastic synovium causes cartilage damage through directed adhesion and invasion, resulting in joint-space narrowing on radiography.

    • Major cartilage damage is caused by MMPs, such as membrane-type I MMP, that degrade type II collagen and glycosaminoglycans.

    • Cartilage does not have enough regenerative potential, and under the influence of synovial cytokines and reactive nitrogen intermediates, chondrocytes undergo apoptosis, leading to cartilage degradation.

    • Bone healing: primary (mechanical strain <2%), secondary (mechanical strain 2-10%), and non-union or delayed union (mechanical strain >10%)

    • Bone fracture healing: intricate process to restore bone to pre-injury state and composition, involves hematoma formation, granulation tissue formation, callus formation, and bone remodeling

    • Fracture healing starts with an anabolic phase, where stem cells are recruited and differentiated, leading to cartilaginous callus formation and primary bone formation

    • Concurrently, angiogenesis occurs, where cells involved are recruited and differentiated, resulting in the mineralization of the extracellular matrix and chondrocyte apoptosis

    • Hematoma formation is a crucial step, where disrupted blood vessels cause clotting and provide a temporary frame for subsequent healing, and MSCs are recruited

    • Granulation tissue formation provides provisional stability, triggers an inflammatory response, and initiates fibrocartilaginous callus formation

    • Callus formation involves the action of various cells, including fibroblasts, osteoblasts, and osteoclasts, to lay down woven bone and calcify the cartilaginous callus

    • Bone remodeling continues for months to years after clinical union, involving the interaction of signaling pathways to differentiate the appendicular skeleton.

    • Women with osteoporosis should begin treatment with risedronate, alendronate, zoledronic acid, or denosumab to reduce the risk of both vertebral and non-vertebral fractures.

    • Bazedoxifene, a selective estrogen receptor modulator combined with conjugated estrogen, is approved by the FDA for osteoporosis prevention but not for treatment.

    • Men should be offered bisphosphonates as the first-line therapy.

    • Teriparatide can be used in patients who cannot tolerate bisphosphonates.

    • Medications, such as raloxifene and ibandronate, which only reduce vertebral fractures, are reserved for patients who cannot tolerate previous medications.

    • Combination therapy of teriparatide and a bisphosphonate or teriparatide and denosumab can be considered for patients with severe osteoporosis and hip and vertebral fractures.

    • There are no randomized studies regarding monitoring of treatment with follow-up dual X-ray absorptiometry scans, but several studies show that women had reduced fractures with treatment independent of follow-up bone mineral density.

    • Agents like teriparatide and hormonal-based therapy require immediate follow-up treatment with another agent upon stopping the medication, or bone mass is rapidly lost.

    • There is ongoing debate about the most beneficial bisphosphonate treatment regimen, with studies underway to determine the benefits of drug holidays after five years of therapy or continuous therapy.

    • Pharmacotherapy agents work through either anti-resorptive or anabolic means and include bisphosphonates, hormone replacement therapy, selective estrogen receptor modulators, teriparatide, and RANKL inhibitors.

    • Bisphosphonates, particularly nitrogen-containing compounds, inhibit farnesyl pyrophosphate synthase, inhibiting osteoclast resorption and inducing osteocyte apoptosis.

    • Common bisphosphonates include alendronate, risedronate, and zoledronic acid, and they reduce the rate of hip, spine, and wrist fractures significantly.

    • Hormonal-based therapy, such as conjugated estrogen-progestin hormone replacement therapy and estrogen-only replacement therapy, can also be used for osteoporosis treatment, but with caution due to the risk of adverse effects.

    • Teriparatide is a recombinant form of parathyroid hormone that stimulates osteoblasts to produce more bone, and is now FDA-approved for osteoporosis treatment in males and females.

    • Denosumab is a monoclonal IgG2 that targets RANKL and inhibits its ability to bind to RANK, inhibiting osteoclast activation.

    • Patients on bisphosphonates for any length of time and presenting with mild thigh discomfort should undergo a thorough workup, including education on the risks of thigh discomfort, full-length femur and hip radiographs, discontinuation of bisphosphonates, and referral to an orthopedic surgeon.

    • Osteoporosis is a significant public health issue, affecting millions of elderly individuals, and is best managed by an interprofessional team of healthcare workers.

    • Patient education is vital, including urging patients to modify their lifestyle and remain compliant with medications, quitting smoking and alcohol, and following a calcium-rich diet and taking vitamin D supplements.

    • The outcomes of osteoporosis are poor, with over 250,000 hip fractures occurring each year and high mortality rates, loss of independence, and poor quality of life.

    • Secondary complications, such as pressure sores, deep vein thrombosis, and nosocomial infections, are common in patients with osteoporosis.

    • Limited sun exposure can lead to vitamin D deficiency and rickets despite year-round sunlight, due to clothing, indoor living, skin color, diet, pollution, or sunscreen use.

    • Prevalence of rickets is higher in developing countries, especially in Africa, Middle East, and Asia, with rates of 10% to 70%.

    • Developed countries saw a decrease in rickets with dietary supplementation, improved air quality, and public awareness.

    • Incidence rates vary widely: 2.9/100,000 eventually 24.1/100,000 in the US, 10.5/100,000 for children under 3 in New Zealand, and 3.8/100,000 in Turkey.

    • Rickets is most common in Alaska due to higher latitudes and lowest sunlight.

    • Rickets is a bone disease caused by defects in the osteoid mineralization process, which results in abnormal growth of the cartilaginous growth plate.

    • Vitamin D is necessary for normal mineralization; it can be obtained through diet or UVB exposure.

    • Low serum calcium and phosphate levels can cause increased parathyroid hormone (PTH), which leads to hypophosphatemia and accumulation of hypertrophic chondrocytes.

    • Evaluation includes serum alkaline phosphatase (ALP), which is high due to phosphate deficiency and increased osteoblastic activity, and serum 25-hydroxyvitamin D level, which is typically low in vitamin D deficiency.

    • Secondary hyperparathyroidism can lead to internalization of phosphate co-transporters in renal tubules, resulting in renal phosphate loss and hypophosphatemia.

    • Phosphopenic rickets is caused by chronic low serum phosphate levels due to impaired intestinal absorption or increased renal loss.

    • Phosphate deficiency is rare in healthy individuals due to abundance in food.

    • Premature children can experience osteopenia of prematurity from dietary phosphate deficiency.

    • Fibroblast growth factor 23 (FGF23) increases renal phosphate loss and decreases reabsorption.

    • Mutations causing inactivation of sodium-dependent phosphate transporters in the kidneys can lead to increased urinary phosphate loss.

    • Both calcipenic rickets and phosphopenic ricks are characterized by hypophosphatemia and rachitic bone changes.

    • Inhibited mineralization rickets occurs due to defects in growth plate mineralization with normal calcium and phosphate levels.

    • Genetic causes of rickets are classified into vitamin D-dependent (calcipenic) and congenital hypophosphatemic types.

    • Vitamin D-dependent rickets (VDDR): caused by defects in vitamin D synthesis, vitamin D receptor, or vitamin D-VDR interactions.

    • VDR mutations in VDDR2A cause end-organ resistance to the active form of vitamin D.

    • FGF-23-dependent hypophosphatemic rickets: characterized by an abnormality in phosphatonin regulation of phosphate homeostasis.

    • FGF-23-independent hypophosphatemic rickets: characterized by a pathology in the renal tubules causing phosphate transport defects.

    • Vitamin D deficiency is the main cause of rickets worldwide in older infants and toddlers.

    • Risk factors for nutritional vitamin D deficiency include prolonged exclusive breastfeeding, excessive juice consumption, and inadequate intake of vitamin D fortified foods.

    • Vitamin D deficiency in pregnant mothers can predispose their babies to rickets and hypocalcemia.

    • Vitamin D deficiency and rickets are more common in higher latitudes due to reduced UVB radiation.

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    Test your knowledge of assessing symptoms and clinical features of musculoskeletal conditions, and differentiating between inflammatory and non-inflammatory joint conditions. Learn to recognize characteristics of inflammatory joint conditions like rheumatoid arthritis (RA) and non-inflammatory conditions like osteoarthritis (OA).

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