Rehab521 Autumn 2024 Lecture 27 Bone and Soft Tissue Disorders PDF

Soft Tissue and Bone Disorders Disorders to be discussed today include: Metabolic bone disease Developmental dysplasia of the hip High mag micrograph of Paget Scoliosis disease of the bone. H&E Ankylosing spondylitis s...

Soft Tissue and Bone Disorders Disorders to be discussed today include: Metabolic bone disease Developmental dysplasia of the hip High mag micrograph of Paget Scoliosis disease of the bone. H&E Ankylosing spondylitis stain. There is a prominent jigsaw-puzzle like pattern. Pathophysiology of tendon, ligament, and cartilage injury and healing Heterotopic ossification Ehlers-Danlos Syndrome (EDS) Adhesive capsulitis Rehab 521: Pathophysiology Radiograph showing a dislocation of the left hip in Mary Beth Brown, PT, PhD Development Dysplasia of the Hip  Metabolic bone disease Is the 3rd most common endocrine disorder, after diabetes and thyroid disorders Refers to a large spectrum of bone disorders, usually with mineral abnormalities (e.g. calcium, phosphorus, magnesium or vitamin D) The more common ones include – osteoporosis – rickets/osteomalacia – fluorosis – primary hyperparathyroidism (PHPT) The rarer ones include – Paget disease – tumor-induced osteomalacia – fibrous dysplasia – osteogenesis imperfecta  Metabolic bone disease Why learn this? Keep in mind: PTs treat many people with osteoporosis as a secondary diagnosis The presence of such a secondary diagnosis may appropriately influence the therapist’s choice of evaluation and intervention, so it is important that you understand these  Metabolic bone disease Osteoporosis (to be discussed in next lecture) Osteomalacia Paget disease  Metabolic bone disease Osteomalacia  Definition of osteomalacia Softening of the bone caused by insufficient mineralization of the bone matrix (the osteoid laid down by osteoblasts) – The problem is in how bone tissue is being constructed – Osteomalacia in children is often referred to as ‘rickets’ (even though, strictly speaking, rickets is due to a vit D deficiency) Normal Remodeling Osteomalacia Remodeling Red=osteoid Green=mineralized  Pathogenesis of osteomalacia Since osteoid fails to mineralize, strength of the bone tissue is reduced – Structure remains, but lack of mineralization leaves the bone softer and less rigid, easy to bend Red=osteoid Green=mineraliz ed bone https://www.orthobullets.com/basic -science/9033/osteomalacia  Pathogenesis of osteomalacia Undermineralized regions of bone appear as radiolucent strips – Visible osteoid seams with reduced mineral content – Also classified as pseudofractures  Pathogenesis of osteomalacia Insufficient intestinal calcium absorption – Reduced calcium availability – Insufficient vitamin D which is required for the intestinal absorption of calcium – Abnormal vitamin D metabolism Increased renal phosphorus loss – Can be associated with kidney disorders – Some tumors can interfere with kidney’s ability to reabsorb phosphorus  Risk factors associated with osteomalacia Older adults – Calcium and vitamin D deficiency – Reduced sunlight exposure – Intestinal malabsorption problems Medications – Excessive antacids (can cause phosphate deficiency) Aluminum hydroxide can bind with phosphate preventing GI absorption of phosphate History of: – Hyperparathyroidism – Chronic renal failure or renal tubular defects  Clinical manifestations of osteomalacia Bone pain – Pain tends to intensify with exercise – Can develop chronic pain Important point regarding bone scan report: – Osteomalacia is commonly misdiagnosed as osteoporosis – Under mineralized regions of bone tissue (osteoid) can be examined histologically (via bone biopsy) and radio-graphically  Clinical manifestations of osteomalacia Softening of bones and muscle weakness can lead to alterations in bone structure, postural deformities, and an increased risk of fractures Long bone bowing https://www.orthobulle ts.com/basic-science/9 033/osteomalacia Proximal femoral neck fx due to osteomalacia  Paget disease Localized disorder of bone remodeling Characterized by aggressive osteoclast mediated bone resorption, followed by imperfect osteoblast bone repair “Pagetic osteoclasts” at affected sites Creates disorganized bone tissue  Paget disease Localized disorder of bone remodeling Characterized by aggressive osteoclast mediated bone resorption, followed by imperfect osteoblast bone repair “Pagetic osteoclasts” at Osteoclasts in normal bone and in Paget’s affected sites disease. (A) Normal osteoclasts are large multinucleated cells that contain between 3 Creates disorganized and 20 nuclei per cell. (B) In contrast, pagetic bone tissue osteoclasts are markedly increased in number ‘Paget disease of bone’ and size and can contain up to 100 nuclei J Clin Invest. https://www.jci.org/articles/view/24281 (arrow).  Paget disease: Etiology Normal Bone Named after British surgeon, Sir James Paget, who first identified the disease in 1877 A condition of unknown cause affecting about 3% of the population over 40 years of age 2nd most common bone disease after osteoporosis Paget’s Bone  Paget disease: Etiology Normal Bone Accelerated bone resorption (by the osteoclasts) makes it hard for the osteoblasts to keep up – Fibrous tissue replaces normal bone tissue, and bone tissue is structurally unorganized making it more likely to fracture Paget’s Bone  Paget disease: Etiology Exact cause is unknown 15-30% of cases have a positive family history Research points to both viral and genetic causes – Viral: paramyxoviral infection (measles virus), virus persists in osteoclasts – Genetic link: mutations found with CSF-1 gene, RANK gene and PML gene Highly related to geographic location – Europe, North America, Australia, New Zealand  Paget disease: Pathology Regions of accelerated bone formation may not be adequately mineralized, resulting in widened osteoid seams Most common sites affected (typically localized): – Pelvis, spine, femur and skull – Can be monostotic (one bone) or polyostotic (few bones) Other complications include osteoarthritis and neurologic complications  Paget disease: Pathology Trabecular bone is replaced by coarse, irregular, thickened trabeculae Cortical bone is irregularly thickened, rough and may be pitted  Paget disease clinical manifestations Skeletal deformity Bowing of long bones Excessive enlargement of skull – May be associated with hearing loss, severe headaches  Paget disease clinical manifestations Bone pain--- usually does not present until late in disease course May worsen with weight- bearing, particularly in regions of osteolytic bone tissue Bone scintigraphy Sudden pain may indicate of a patient fracture with Paget disease: Affected bone may feel warm involved the entire skull due to hypervascularity and the right Paget's Disease of Bone: Diagnosis and hemipelvis Treatment The American Journal of Medicine (arrows) Volume 131, Issue 11, November 2018 https://www.sciencedirect.com/science/article/pii/S0002934318304 054  Paget disease clinical manifestations Changes in cortical bone tissue in a women with Paget disease from 45 to 68 years See notes section for caption  Paget disease clinical manifestations No cure at present – Important to start treatment program during early disease stages Goal is to manage bone loss and deformity Bisphosphonates to reduce osteoclast activity If bisphosphonates are not tolerated, calcitonin can be given Pain medications and non-pharmacologic interventions (e.g. PT) to help manage pain and maintain mobility Paget's Disease of Bone: Diagnosis and Treatment The American Journal of Medicine Volume 131, Issue 11, November 2018 https://www.sciencedirect.com/science/article/pii/S0002934318304 054  Soft Tissue and Bone Disorders Disorders to be discussed today include: Metabolic bone disease Developmental dysplasia of the hip Scoliosis Ankylosing spondylitis Pathophysiology of tendon, ligament, and cartilage injury and healing Heterotopic ossification Ehlers-Danlos Syndrome (EDS) Adhesive capsulitis Rehab 521: Pathophysiology Mary Beth Brown, PT, PhD Developmental Dysplasia of the Hip Common developmental process that occurs either in utero or during the first year of life – In utero and post-birth malposition of the baby – Early instability of the hip joint causing dysplasia 3 levels of severity – Unstable hip dysplasia – hip is positioned normally but is prone to dislocation by manipulation – Subluxation or incomplete dislocation – femoral head remains in contact with the acetabulum, but is partially displaced or uncovered – Complete dislocation – femoral head is totally outside the acetabulum  Risk Factors, Signs and Symptoms Incidence: ~8.6 to 11.5 per 1000 live births (85% girls) Risk Factors: – Presence of certain maternal Breech obstetric conditions position Breech delivery, large neonate, at birth twin or multiple births – Infant conditions: Idiopathic scoliosis, myelomeningocele (spina bifida), arthrogryposis, cerebral Asymmetr palsy ic Signs/Symptoms: movemen – Physical asymmetries in ROM t of hips (especially hip abduction) – Asymmetry in the buttock or gluteal fold (higher on the affected side) – Extra thigh skin folds  Treatments Available Conservative Pavlik harness, hip spica cast *Immobilization at least 6-8 weeks – promote proper bone growth of Surgical acetabulum and positioning Post-op Dysplastic roof of acetabulum, head of femur dislocated See caption in NOTES section  Scoliosis An abnormal lateral curvature of the spine Classifications: – Idiopathic – unknown cause; 80% of all cases – Osteopathic – spinal disease or bony abnormality – Myopathic – muscle weakness – Neuropathic – central nervous system disorder Higher incidence: cerebral palsy, spina bifida, neurofibromatosis, muscular dystrophy  Scoliosis Most cases of progressive idiopathic scoliosis diagnosed in adolescence (ages 5-11 girls, 5-13 for boys) Development is associated with growth velocity of the spine – Infantile idiopathic scoliosis – thoracic, toward the left – Juvenile idiopathic scoliosis – right thoracic Severe curves curvature (most common) may affect rib cage (ventilation), Cobb angle – via thoracic and imaging, used to abdominal organs determine severity and prescribe treatment(s)  Etiology After Adolescence Structural (infantile, juvenile) vs. Functional Functional (postural) scoliosis caused by factors other than vertebral involvement – Pain, poor posture, leg-length discrepancy, muscle spasm (examples in figure; from herniated disc, spondylolisthesis, etc.) – Curve disappears when the cause is remedied – Can become structural if untreated  Ankylosing Spondylitis (AS) An autoimmune, inflammatory arthropathy of the axial skeleton, sacroiliac joints, apophyseal joints, costovertebral joints, and intervertebral disk articulations Can progress to fibrosis, calcification, and ossification with fusion of involved joints Figure 27-20: Joints most commonly involved (and incidence) – Virtually all have sacroiliac (SI) involvement  AS Signs and Symptoms Enthesitis – Inflammation of the tendons, ligaments, and capsular attachments to bone Tenderness, pain and/or stiffness, restricted mobility – Early stages: Pain described as a Sacroiliac joint biopsy specimen of a 29 year old dull ache that is poorly localized male patient with AS – Later stages: Pain can become severe and constant, increased by prolonged rest or immobility and decreased by active movement Morning stiffness, lasting > 1 hour Pharmacological management – NSAIDs – In some cases immunosuppressant drugs – DMARDs- such as methotrexate  Progression Early stage s Long-standing disease (over many years) is associated with: Many years Loss of chest wall excursion  difficulty breathing and fighting pulmonary infections Aortic enlargement, aortic valve changes Eye inflammation (uveitis) Skeletal complications: osteoporosis, fractures, atlantoaxial subluxation, spinal stenosis Late stage Late stages – severe s fusion in a rigid upright or stooped position  Case Study- Ankylosing Spondylitis (AS) 28-year-old male with acute on chronic diffuse low back pain for years. Recent exacerbation due to injury while weightlifting Referred to PT by PCP after physical exam and reports difficulty with sitting, weightlifting and significant morning stiffness that takes one to several hours to decrease. Patient with improvement in symptoms with physical therapy after 6 visits with almost complete resolution of symptoms and return to full activity participation. However, reports no change in morning stiffness (lasting 2-4 hours) and exercises that were helping his acute flare up, did not change morning stiffness When asked further, Patient reports that morning stiffness started 4-5 years ago when he was in the military and has been present every day since, denies specific injury. PT messaged MD regarding concern of ankylosing spondylitis. – PCP ordered x-ray and labs which were + for ankylosing spondylitis and patient was referred to rheumatology. – Patient started DMARDs and reported significant improvement in morning stiffness. – Saw PT for 1-2 additional sessions to discuss management of AS and treatment plan, then discharged to self-management  Soft Tissue and Bone Disorders Disorders to be discussed today include: Metabolic bone disease Developmental dysplasia of the hip Scoliosis Ankylosing spondylitis Pathophysiology of tendon, ligament, and cartilage injury and healing Heterotopic ossification Ehlers-Danlos Syndrome (EDS) Adhesive capsulitis Rehab 521: Pathophysiology Mary Beth Brown, PT, PhD Soft Tissue Injuries – Tendon Tendonitis/tendinosis: – Tendon is most vulnerable to injury when it is tense (eg. the attached muscle is maximally contracted) – Chronic inflammation, recurrent stress  tendinosis (see later slides about this) Tendon rupture: – Common injuries: patellar tendon, supraspinatus tendon, medial and lateral epicondyles, Achilles tendon – Achilles: Inciting event often is an athletic activity that requires a sudden acceleration or changes in direction (eg. basketball, soccer) Soft Tissue Injuries – Tendon Classification of Injury First-degree injury (Grade I, mild tear) – Stretching or minor tearing of a few fibers without loss of integrity, with only minor swelling and discomfort Second-degree injury (Grade II, moderate tear) – Partial tearing of tissue with clear loss of function. Pain, moderate disability, point tenderness, swelling, localized hemorrhaging Third-degree injury (Grade III, severe tear) – Complete loss of structural or biomechanical integrity extending across the entire cross section of the tendon/ligament and usually requiring surgical repair Soft Tissue Injuries Cartilage tear – Knee cartilage tears are most common – Mechanical etiology by twisting motion while weight-bearing Ligament sprain – Sprain – an injury of the ligamentous structures around a joint – Usually caused by abnormal or excessive joint motion  Soft tissue injuries ‘The spatio‐temporal Ligament dynamics of ligament healing healing’ involves a Chamberlain et al 2009 coordinated series of inflammation -driven events that form a neo‐ ligament which is more scar‐like in character than the native tissue How do we know this time course of events? https://doi.org/10.1111/j.1524-475X.2009.  Soft tissue injuries Experimental models (animals, ex- vivo, model systems, etc) where events are measured hourly/daily For example: Inflammatory cells measured over days after an experimental animal ligament injury. See full caption in notes section How do we know this time course of events? https://doi.org/10.1111/j.1524-475X.2009.  Soft tissue injuries Experimental models (animals, ex- vivo, model systems, etc) where events are measured hourly/daily For example: Angiogenic pattern of the healing medial collateral ligament (MCL). Microangiography of the (A) normal; (B) 1 day; (C) 3 days; (D) 5 days; (E) 7 days; (F) 9 days; (G) 11 days; (H) 14 days; (I) 21 days; or (J) 28‐day postinjured ligament. Scale bar: 2.0 mm. Original magnification × 40. How do we know this time course of events? https://doi.org/10.1111/j.1524-475X.2009.  Soft tissue injuries The remodeling phase process may extend from months to years and the injured ligament never fully recovers its original mechanical properties  Soft tissue injuries The ‘Biomechanics of tendon injury and repair’ remodeling phase process may extend from months to years and the injured tendon never fully recovers its original mechanical https://www.scienc Journal of Biomechanics properties edirect.com/scienc e/article/pii/S00219 Volume 37, Issue 6, June 29003004068?via %3Dihub#FIG6 2004,  Soft tissue injuries Motion has been shown to promote cellular activity ‘Biomechanics of tendon injury and repair’ and minimize adhesion formation It should not be applied at the expense of a potential rupture A fine balance exists between the progression of healing and applying mobilization Experimental data can be used to create a clinical rehabilitation protocol, which consists of a combination of immobilization and activity https://www.scienc that allows for optimal edirect.com/scienc Journal of Biomechanics healing e/article/pii/S00219 Volume 37, Issue 6, June 29003004068?via %3Dihub#FIG6 2004,  Soft tissue injuries Normal Tendinosis is associated with anatomical & physiological changes in the tendon structure and organization Tendinosi s NATure revIewS | DISEASE PRIMERS | Article citation ID: (2021)7:1  Tendinos is Proposed mechanisms of tendinosis- associated NATure revIewS | DISEASE PRIMERS | Article citation ID: changes  Tendinos is Proposed mechanisms of tendinosis- associated NATure revIewS | DISEASE PRIMERS | Article citation ID: (2021)7:1 changes  Tendinos is NATure revIewS | DISEASE PRIMERS | Article citation ID: (2021)7:1  Heterotopic Ossification (HO) Bone formation in non- osseous tissues (ectopic) Risk factors: – Serious traumatic injury (fractures, surgery, SCI, TBI, burns, amputation) Heterotopic Ossification on – Previous history of HO Imaging – Certain disorders, e.g. Hypertrophic osteoarthritis, Ankylosing spondylitis (AS), Diffuse idiopathic skeletal hyperostosis Most common complication of total hip arthroplasty O in muscle is AKA ‘myositis ossificans’ Histology of mature/late‐  Heterotopic Ossification (HO) Association between the severity of injury and amount of ectopic bone formation – Multifactorial etiology and treatments still being investigated – Pluripotent mesenchymal (AKA ‘stem’) cells become osteoblasts instead of soft tissue – Specific immune cells Fig. 4: Single cell RNA (monocytes/macrophages sequencing reveal multiple ) may regulate trauma- monocyte and macrophage clusters Sorkin etduring al. Nattrauma induced induced HO and aberrant Commun, HO. 2020. chondrogenic progenitor cell differentiation Mechanisms of HO after TBI A diagram of possible mechanisms of the development of heterotopic ossification after traumatic brain injury Huang et al. J Orthop Translat. 2017.  Ehlers-Danlos Syndrome (EDS) Ehlers-Danlos Syndrome: inherited disorders that affect connective tissue – Classic characteristics: Joint hypermobility – Can lead to dislocations, subluxations, sprains, joint instability – Observed in most types of EDS, may be limited to hands and feet Skin hyperextensibility Tissue fragility – Can lead to poor wound healing – Prevalence 1 in 3000 to 5000 people have all types of EDS Hypermobility EDS (hEDS) is the most common, 1 in 600 to 9000 people, and often underreported, other types are significantly less prevalent Most subtypes have genetic influence, however for hEDS this is less understood.  EDS 13 different subtypes – Vascular EDS can be life threatening due to vascular hemorrhage – hEDS (hypermobil e) is the most common FYI- no need to memorize all the types, just know that  EDS: Assessment Brighton Scale: 9 point scale that is part of the diagnostic criteria for EDS – Positive: 6+ criteria for pre-pubertal children and adolescents 5+ for pubertal men and women less than 50 years old 4+ for those over 50 years oldtofor FYI- no need hEDS memorize  hEDS vs. Hypermobility Spectrum Disorder (HSD) https://ehlersdanlosnews.com/health-insights/hy permobile-eds-vs-hypermobility-spectrum-disord Major difference: hEDS has stricter ers/ diagnostic criteria – Updated diagnostic criteria in 2017 gave more specifics for hEDS that requires positives in 3 different areas of symptoms. Previously diagnosis was based on skin and joint involvement. There is no genetic cause identified yet Ranging clinical spectrum, can be asymptomatic or a wide range of symptoms – Some include: sleep disturbances, fatigue, POTS, Functional GI disorders, anxiety, depression, debilitating joint pain Differentiation between hEDS and HSD is more important for research, treatment is based on symptom management See figure caption in  EDS: Treatment No solid evidence-based EDS-specific treatments yet Depending on type of EDS, may need to work with multiple different providers – For vascular EDS, will need to have cardiac work-up (Echo) in order to examine vessels and work on decreasing stress to the aorta and arteries. – Medically managing pain, high BP and cholesterol is important. PT implications – Easy to perform the Brighton Index if you have concerns – Education on joint protection strategies during daily tasks – Strength and balance training to help with joint pain and protection – Patients may be prone to joint dislocations and subluxations  Adhesive Capsulitis AKA: ‘Frozen Shoulder’ Characterized by painful and gradual loss of shoulder range of motion that is spontaneous or due to trauma  Adhesive Capsulitis Symptoms are due to inflammatory and fibrotic changes to the synovial fluid in the capsule and bursa of the shoulder Capsule volume shrinks, adhesions are present Natural hx of 15-18 mo for relative return to function 20-50% of people have lasting limitations Still not 100% sure on the underlying pathophysiology but have a much better understanding when able to look at more inflammatory markers  Adhesive Capsulitis Proposed sequence of alterations in the development of frozen shoulder. Frozen Shoulder: A Systematic Review of Cellular, Molecular, and Metabolic Findings JBJS Reviews9(1):e19.00153, January Just FYI  Adhesive Capsulitis Treatment: non-surgical for pain management and aiming to keep range of motion, can have surgical options for manipulation under anesthesia (MUA), or to increase capsule space (capsulotomy)  Diabetes and Adhesive Prevalence: Capsulitis – In a population with DM, adhesive capsulitis was 30%. – In a population of adhesive capsulitis, DM was 13.4% – Diabetic patients are 5x more likely to have adhesive capsulitis – No significant differences between Type 1/type 2 or type of glycemic control May be due to underlying changes in tendon stiffness and tissue changes as observed in diabetic mice studies. Additionally, chronic inflammation can lead to increase collagen and ECM components