Musculoskeletal
N609

Osteoarthritis (OA) is a progressive disease that can result in chronic pain, restricted range of motion, and muscle weakness, especially if a weight-bearing joint is affected.
The joints commonly affected by OA include the knees, hips, cervical and lumbar spine, distal interphalangeal (DIP) joints, and the carpometacarpal joint at the base of the thumb.

Primary, or idiopathic:
Arises from physiologic changes that occur with normal aging.
Secondary:
Usually results from traumatic injuries or inherited conditions and may present as hemochromatosis, chondrodystrophy, or inflammatory OA.

Modifiable
Obesity; prior joint injury
Occupations requiring excessive mechanical stress or heavy lifting
Nonmodifiable
Gender, age, race, genetics

OA must be differentiated from other forms of arthritis because the physiologic changes specific to the condition dictate disease management.
Although most forms of arthritis, including OA, result in degeneration of articular cartilage, the subsequent formation of new bone is a change specific to OA.

Hand: Pain, aching, or stiffness and three of the following:
Hard tissue enlargement of >2 joints; Hard tissue enlargement of >2 DIP joints; <3 swollen metacarpophalangeal joints; deformity of >1 selected joint
Hip: Pain and two of the following:
Erythrocyte sedimentation rate (ESR) <20 mm/h; Radiographic femoral or acetabular osteophytes; Radiographic joint space narrowing
Knee: Knee pain and three of the following:
>50-year-old; stiffness <30 minutes; crepitus; bony tenderness

Clinical and radiographic diagnosis: Knee pain + osteophytes and one of the following:
>50-year-old; stiffness <30 minutes; crepitus
Bony enlargement; no palpable warmth
Clinical and laboratory diagnosis: Knee pain and five of the following:
Age >50 years; stiffness <30 minutes; crepitus; bony tenderness; bony enlargement; no palpable warmth; ESR <40 mm/h; RF <1:40; synovial fluid signs of OA (clear, viscous, or WBC count <2,000/mm3)

Before initiating drug therapy, the practitioner should recommend appropriate physical activity or physical therapy.
The goals in managing osteoarthritis are to reduce pain, improve motion, and maintain functional ability.

Topical therapy is preferred over systemic therapy by the European League Against Rheumatism (EULAR) and the Osteoarthritis Research Society International (OARSI).
Topical nonsteroidal antiinflammatory drugs (NSAIDs) are strongly recommended by the American College of Rheumatology (ACR) for knee osteoarthritis and conditionally for hand osteoarthritis. Due to concerns with absorption in hip osteoarthritis, topical therapy is typically not recommended.
Systemic therapy may be more effective depending on the number and location of joints affected. Topical therapy is an attractive option due to the relatively benign side effect profiles.

Second-line therapy for OA includes oral NSAIDs.
NSAIDs are further classified according to their chemical structure. Although these classes have subtle differences, they all exhibit cyclooxygenase (COX) inhibition.

A practitioner is prescribing a medication for a patient recently diagnosed with OA. What is the recommended first line of treatment for OA?
A. Cox-2 selective NSAID
B. Salicylic acid NSAID
C. Acetaminophen
D. Nonacetylated salicylates

C. Acetaminophen
Rationale: First-line pharmacotherapy for OA is geared toward analgesia, specifically with acetaminophen (Tylenol). Due to acetaminophen's cost effectiveness and safety, it is currently the first-line treatment recommended in guidelines by the ACR, the EULAR, and others.

Nonacetylated salicylates are especially beneficial in patients who are sensitive to the gastrointestinal irritation caused by long-term aspirin use.
Diflunisal (Dolobid), the most commonly used nonacetylated salicylate, is an effective COX-1 inhibitor with antiinflammatory and analgesic properties, but its antipyretic activities are weak.

Acetaminophen (Tylenol) is conditionally recommended by the 2019 ACR guidelines and considered an option by the EULAR recommendations due to its possible efficacy and relatively safe side effect profile and affordability.
Acetaminophen is not recommended in the 2019 OARSI guidelines due to questionable efficacy and risk for hepatotoxicity.
It is however an option in patients with limited pharmacologic options due to intolerance or contraindications to the use of NSAIDs. Acetaminophen is best used for short-term infrequent use.

When the pain associated with OA progresses and is no longer responsive to acetaminophen or NSAIDs, analgesics are an option.
Analgesics can also be used in patients who cannot tolerate acetaminophen or NSAIDs or in whom they are contraindicated. Analgesics only decrease pain and have no effect on inflammation.

If symptoms of OA are restricted to one or two joints that have not responded to first- or second-line treatment, intra-articular corticosteroids may be helpful.
The 2019 ACR guidelines generally recommend against the use of intra-articular hyaluronic acid, largely due to limited evidence of benefit and the potential for harm. However, hyaluronic acid may be considered in patients who do not find satisfactory relief or after alternatives have been exhausted.

Gout is an inflammatory condition that results from monosodium urate crystals precipitating in the synovial fluid between joints due to hyperuricemia.
The monosodium urate crystals form due to hyperuricemia either from overproduction or from under-excretion of uric acid.
The most common joint affected is the metatarsophalangeal joint.
Other common affected joints include the midtarsal joints, ankles, knees, fingers, wrists, and elbows.

Diagnosis of gout usually occurs clinically when a patient is experiencing rapid monoarticular arthritis, typically in the first metatarsophalangeal joint. This arthritis is accompanied by swelling and redness of the joint.

The treatment of gout can be divided into treatment of chronic gout and treatment of acute gout attacks.
The goals of drug therapy in chronic gout are to decrease the serum urate level to less than 6 mg/dL and to decrease the occurrence of acute gout attacks.
The goal of less than 5 mg/dL may be preferred in patients with multiple risk factors or with a history of frequent acute gout attacks.
Decreasing the serum urate level will help to reach the clinical goal of less pain and inflammation in the joints.
For an acute gout attack, the goals are to relieve pain, terminate the attack, and maintain joint function.

Urate-lowering therapies (ULT) are the primary pharmacologic treatment for chronic gout. Often, gout flares can occur when initiating ULT due to the redistribution of uric acid.
To prevent these gout flares, patients should take NSAIDs or colchicine for the first 6 months of therapy.
After 6 months, the number of gout flares should decrease due to the initiation of ULT. At this time, NSAIDs and colchicine can be discontinued until they are required for gouty flares.

Allopurinol has been used as first-line therapy among clinicians for decades.
When febuxostat became Food and Drug Administration approved for chronic gout treatment in 2009, many expert clinicians viewed it as an attractive, alternative agent to allopurinol without the risk of hypersensitivity reaction or the need for a renal dose adjustment.

If at least one XOI is contraindicated or not tolerated well, practitioners should use probenecid for the treatment of chronic gout.
The 2012 update to the ACR guidelines also recommends the addition of probenecid to a XOI if serum uric acid levels are not at goal with a XOI alone.

Pegloticase is used as last-line therapy for patients with chronic gout that has not successfully been treated with either XOIs or probenecid.
It must be administered intravenously in a health care facility every 2 weeks and costs more than $5,000 per dose.

Patients with chronic gout will commonly experience gout attacks.
Making dietary modifications and discontinuing the usage of medications that can induce gout attacks, weight loss, and controlling other diseases states will help decrease the frequency of attacks, but they will occur in gout patients.
When an acute gout attack occurs, patients can rest the joint and apply ice as needed to help with pain. They can also use short courses of NSAIDs, corticosteroids, or colchicine to reduce pain.

Patient-Oriented Information Sources
Nutrition/Lifestyle Changes
Complementary and Alternative Medicine

OA, formerly known as degenerative joint disease, is the most common joint problem in the United States. Based on U.S. data from 2005, OA affects approximately 14% of adults older than age 25 and one third of adults older than age 65.
Gout is the most common form of inflammatory arthritis in the United States. The incidence of gout in America has increased over the last 20 years and is now estimated to affect 8.3 million Americans (4%). This increase is thought to be due to not only improved diagnosis but also the increasing number of patients with obesity, hypertension, thiazide diuretic use, and alcohol intake.

Osteoporosis is a progressive systemic disease characterized by a decrease in bone mass and microarchitectural deterioration of bone tissue, resulting in bone fragility and increased susceptibility to fractures.
Bone fracture is the major cause of mortality and morbidity in patients with osteoporosis.

Vertebral compression fractures
Fractures of the distal radius
Fractures of the proximal femur

Type I: Postmenopausal Osteoporosis
Occurs in postmenopausal women between ages 51 and 75.
Decreased estrogen causes an accelerated rate of bone loss, especially trabecular bone loss.
The most common fractures are of the vertebrae and distal femur. There is also tooth loss.

Type II: Senile Osteoporosis
Occurs in men and women older than age 70.
There is a proportional loss of cortical and trabecular bone.
The most common fractures are hip, pelvic, and vertebral.

Type III: Secondary Osteoporosis
Occurs in men and women at any age
Secondary to other conditions such as drug therapy and other diseases

For which patient would a diagnosis of type III osteoporosis be considered?
A. A postmenopausal woman who fractures a femur
B. A 75-year-old man who breaks a hip
C. A 45-year-old woman who takes medicine for hyperparathyroidism
D. A 60-year-old woman who is experiencing tooth loss

C. A 45-year-old woman who takes medicine for hyperparathyroidism
Rationale: Type III: secondary osteoporosis occurs in men and women of any age and is secondary to other conditions such as drug therapy and other disease. A 75-year-old man who breaks a hip may have type II: senile osteoporosis. A postmenopausal woman experiencing fractures and tooth loss may have type I: postmenopausal osteoporosis.

Female sex; older age; Asian or white race
Family history; petite stature; low body weight
Amenorrhea, menopause
Sedentary lifestyle; low calcium intake
Excess alcohol intake; smoking; excess caffeine intake
Low testosterone level in men
Certain drugs and disease states

All women older than age 65 and men over 70
Younger perimenopausal or postmenopausal women and men who have any medical condition or are taking medication associated with bone loss
Any adult older than age 50 with a fracture
Anyone being treated for osteoporosis
Men age 50 and older at risk

FRAX
Ten risk factors considered in addition to the bone mineral density (BMD) T-score: age, gender, fracture history, parental hip fracture history, oral steroid therapy, low body mass index, femoral neck BMD, secondary osteoporosis, current smoking, and alcohol intake.
"WHO Fracture Risk Assessment Tool"

Low bone mass (T-score from -1.0 to -2.5 at the femoral neck, total hip, or spine) and 10-year probability of hip fracture of 3% or more or a 10-year probability of any major osteoporosis-related fracture of 20% or more.
T-score of 2.5 or less at the femoral neck, total hip, or spine after appropriate evaluation to exclude secondary causes.
Low bone mass (T-score from -1.0 to -2.5 at the femoral neck, total hip, or spine) and secondary causes associated with high fracture risk (such as glucocorticoid use or immobilization).

A hip or vertebral (clinical or morphometric) fracture
Other prior fractures and low bone mass (BMD T-score from -1.0 to -2.5 at the femoral neck, total hip, or spine)

Minimizing bone loss
Delaying the progression of osteoporosis
Preventing fractures and fracture-related morbidity and mortality

Alendronate (Fosamax): Prevention: 5 mg/d or 35 mg once a week; treatment: 10 mg/d or 70 mg once a week
Risedronate (Actonel): 5 mg/d or 35 mg once a week
Ibandronate (Boniva): 2.5 mg PO QD or 150 mg PO once a month or 3 mg/3 mL IV every 3 months
Zoledronic acid (Reclast): 5 mg/100 mL once daily

Selective Estrogen Receptor Modulators: Raloxifene (Evista) 60 mg QD
RANK Ligand Inhibitor: Denosumab (Prolia): 60 mg subq every 6 months
Other: Calcitonin (Miacalcin) 200 U (1 spray) daily 100 U IM or SC daily
Hormone modifiers: Teriparatide (Forteo) 20 mcg daily SC

A practitioner is prescribing Fosamax for a patient with osteoporosis. What is the recommended dosage for treatment?
A. 10 mg/d
B. 5 mg/d
C. 2.5 mg/d
D. 60 mg QD

A. 10 mg/d
Rationale: The bisphosphonate alendronate (Fosamax) is dosed; Prevention: 5 mg/d or 35 mg once a week; and Treatment: 10 mg/d or 70 mg once a week.

First line
Prevention: raloxifene, alendronate, ibandronate, zoledronic acid, or risedronate plus calcium and vitamin D
Treatment: raloxifene, alendronate, risedronate, ibandronate, zoledronic acid, or calcitonin
Second line
Addition of hormone modifiers or calcitonin if not being taken

A practitioner is prescribing a second-line treatment for a patient whose osteoporosis is not responding to the first line. What drug would be added?
A. Raloxifene
B. Alendronate
C. Zoledronic acid
D. Hormone modifier

D. Hormone modifier
Rationale: The first line of treatment is raloxifene, alendronate, risedronate, ibandronate, zoledronic acid, or calcitonin. The second line of treatment is to add a hormone modifier or calcitonin if not being taken.

Drug information
Bisphosphonates should be taken with 8 ounces of water, and the patient should remain upright for 30 minutes after administration.
Lifestyle/nutritional changes
Well-balanced diet and weight-bearing exercises
Complementary and alternative therapy
Supplemental calcium and vitamin D

Osteoporosis, or low bone mass (osteopenia), is estimated to occur in approximately 54 million Americans aged 50 years and older, 80% of whom are women.
Women are more likely than men to develop osteoporosis because of thinner, lighter bones, changes associated with menopause, and greater longevity than men.
The NOF recommends that healthcare providers should consider U.S. Food and Drug Administration (FDA)-approved medical therapies for patients at risk for the disease.

Chronic autoimmune inflammatory disease characterized by symmetric polyarthritis and joint changes, including erythema, effusion, and tenderness.
The course of rheumatoid arthritis (RA) is characterized by remissions and exacerbations.
RA can affect several organs, but it usually involves synovial tissue changes in the freely movable joints (diarthroses).

Genetic factors
Infectious agents
Environmental factors
An antigen-antibody response

The synovium becomes more vascularized, and proliferation and hypertrophy begin.
This results in the synovial tissue becoming edematous and exhibiting frond-like villi.
As leukocytes proliferate, the synovial fluid becomes less viscous.

Continued hyperplasia and hypertrophy of the synovial lining occur.
The thickness of the synovial lining increases up to fivefold from the normal one or two cell layers.
The proliferation of the synovium persists, with lymphocytic tissue and plasma cells forming around blood vessels.
This proliferative tissue extends into the joint space, joint capsule, ligaments, and tendons.

Pannus forms as a result of the release of lysosomal enzymes.
This destructive process begins at the synovium and extends to the unprotected area at the junction of the cartilage and subchondral bone.
These inflammatory cells can erode surrounding tissue, tendons, and cartilage.
With pannus invasion, decreased range of motion and ankylosis may ensue. Pannus is a specific feature of RA, differentiating it from other forms of arthritis.

Reducing pain, stiffness, and swelling
Preserving mobility and joint function
Preventing further joint damage

Nonsteroidal anti-inflammatory drugs (NSAIDs) are typically used to help relieve immediate pain and improve symptoms during the diagnostic process.
These agents are continued through the initiation of a disease-modifying antirheumatic drug (DMARD) to maintain reduced symptoms.

Low-dose corticosteroids (<prednisone 10 mg or equivalent) are beneficial in patients who are beginning DMARD therapy.
Because the therapeutic effect of DMARDs may not be seen until several weeks to months after initiating therapy, corticosteroids may be used to provide almost immediate symptom relief and bridge patients until DMARDs take effect.

Early initiation of DMARD therapy may be the best course of action to take in meeting the long-range goals of treatment.
DMARD therapy should be initiated within 3 months after onset of symptoms, if not immediately after diagnosis
Methotrexate
Sulfasalazine
Antimalarials
Leflunomide

A practitioner is prescribing Humira for a patient with RA. What is the recommended dosage?
A. 50 mg SQ monthly in combination with methotrexate
B. 400 mg SQ at weeks 0, 2, and 4 and then 200 mg every other week
C. 100 mg SQ daily
D. 40 mg SQ every other week

D. 40 mg SQ every other week
Rationale: The recommended dosage for Humira is 40 mg SQ every other week; 40 mg weekly as monotherapy. The dosage for Simponi is 50 mg SQ monthly in combination with methotrexate, for Cimzia is 400 mg SQ at weeks 0, 2, and 4 then 200 mg every other week, and for Kineret is 100 mg SQ daily.

A practitioner is prescribing an agent for a patient with RA who failed phase I treatment. What would be the recommended therapy?
A. Methotrexate monotherapy
B. Leflunomide
C. Sulfasalazine
D. bDMARD

D. bDMARD
Rationale: Upon failure of phase I, with poor prognostic factors: bDMARD is recommended, without poor prognositic factors changing csDMARDs is recommended. Treatment for phase I is methotrexate monotherapy or combination; if contraindication to methotrexate: leflunomide or sulfasalazine alone or combination.

Tofacitinib was the first tsDMARD available and targets JAK activity.
Other JAK inhibitors include baricitinib and upadacitinib.

Biologic agents are developed from living sources, such as humans, animals, or microorganisms.
The introduction of various biologics effective against RA has changed the management of RA.
These agents target multiple components involved in the pathogenesis of RA, such as TNF-alpha, T-cell activation, IL-1, and IL-6.
Prior to initiating bDMARDs, patients should be screened for latent TB and hepatitis B due to the increased risk of reactivation.

Women with RA who plan on having children need to discuss treatment options with their physician and understand the risks of conception.
Certain medications, including methotrexate, leflunomide, abatacept, and rituximab, cannot be used during pregnancy because of known teratogenicity

Caution should be used when starting elderly patients on NSAIDs due to the increased risk of gastrointestinal (GI) hemorrhage.
Many elderly patients have decreased renal function, and NSAIDs may contribute to a decline in this function.
Several DMARDs and some immunomodulators are renally excreted, and doses should be adjusted in the elderly due to decreased renal function.

Include baseline studies against which later results can be compared:
CBC with differential
Urinalysis; creatinine
Serum bilirubin, liver enzymes
Erythrocyte sedimentation rate (ESR), blood urea nitrogen (BUN), platelet studies
Eye examinations

Drug information
Necessary blood work
Patient-oriented information sources
Nutrition/lifestyle changes
Complementary and alternative medications

In 2008, approximately 0.6% of the adult population in the United States had RA, with the prevalence in women about twice of that in men (Helmick et al., 2008). New onset of RA is seen throughout the life span, including infancy, but most cases occur in the fifth or sixth decade.
Previous data have shown that patients with RA have a higher rate of disability and mortality compared to patients of similar age without RA. However, with the increased use of DMARDs, especially early in the disease process, these risks appear to have normalized (Kroot et al., 2000).