​Kembara Xtra - Medicine - Osteoporosis and Osteopenia

​Kembara Xtra - Medicine - Osteoporosis and Osteopenia 
A skeletal condition marked by reduced bone mass and disrupted bone architecture that compromises bone strength and increases the risk of fracture


Epidemiology 

 The majority of people are above 60 years old.
 Female is more prevalent than male (80%/20%)
Incidence
In the US, osteoporosis is believed to be a contributing factor in over 2 million fractures each year.
Prevalence
More than 9.9 million Americans have osteoporosis, and more than 43.1 million have osteopenia.
Women over 50 have osteopenia (51.4%) and osteoporosis (15.4%).
 In men over 50, osteoporosis occurs in 4.3% and osteopenia in 35.2%.


Pathophysiology and Etiology 
Hypoestrogenemia; imbalance between bone production and resorption
More common among Caucasians and Asians than in African Americans and Hispanics due to genetics and familial propensity


Risk Factors that Cannot Be Modified
Age >65 years, Caucasian or Asian race, female gender, and menopause, family history of osteoporosis, and history of fragility fractures
• Modifiable:
- Low body mass index (BMI) of 21 or less.
- A lack of calcium and vitamin D - Insufficient exercise - Smoking - Excessive alcohol consumption (more than three drinks a day)
- A range of drugs

Basic Prevention 

Exercise that involves lifting weights on a regular basis. A diet that contains enough calcium (1,000 mg for men 50 to 70 years old and 1,200 mg for women 51 and older and men 70 and older) and vitamin D (800 to 1,000 IU per day).
Prevent smoking.
Limit your alcohol intake to three drinks each day.
Fall prevention (evaluation of home safety, treatment of vision impairment)
(USPSTF guidelines) Display:
- Using the World Health Organization's [WHO] Fracture Risk Assessment [FRAX] Tool, women over 50 with a 10-year risk of a major osteoporotic fracture had a risk of fracture of >8.4% of all women under 65.
- The National Osteoporosis Foundation advises monitoring males over 70, especially if they are at elevated risk, even though there is little evidence to support this recommendation.
- Repeating bone mineral density (BMD) testing 4–8 years after the original screening has not been shown to significantly improve fracture prediction.

Accompanying Conditions 
Malabsorption syndromes include gastrectomy, inflammatory bowel disease, celiac disease; hypoestrogenism includes menopause, hypogonadism, eating disorders, etc.; endocrinopathies include hyperparathyroidism, hyperthyroidism, hypercortisolism, and diabetes mellitus; hematologic disorders include sickle cell disease, multiple myeloma, thalassemia, and hemochromatosis; and
Chemotherapy drugs, antiepileptic drugs, aromatase inhibitors (raloxifene), chronic corticosteroids (equivalent to at least 5 mg of prednisone daily for at least 3 months), medroxyprogesterone acetate, heparin, SSRIs, thyroid hormone (at supraphysiologic dosages), and PPIs are among the medications.

Review the modifiable and non-modifiable risk factors to make a diagnosis.

clinical assessment 

 Historical height loss >4 cm (difference between present height and peak height at age 20 years); thoracic kyphosis; poor balance; deconditioning
 A projected height decrease of more than 2 cm (the difference between the current height and the previously recorded height)


Differential Diagnosis: Osteomalacia; Type I Collagen Mutations; Multiple Myeloma/Other Neoplasms

Initial test results from the laboratory and imaging
The gold standard for calculating BMD and diagnosing osteoporosis is dual energy x-ray absorptiometry (DEXA) of the lumbar spine/hip.
- Osteoporosis can be identified by a BMD at the hip or lumbar spine that is >2.5 standard deviations below the mean BMD reference.
- For a change in BMD to be accurately measured, at least two years may be required.
- T-scores and Z-scores are two metrics used to express BMD:
The T-score represents the amount by which a patient's BMD deviates from the mean.
According to the WHO, a T-score of 1 indicates normal BMD, a T-score between 1 and 2.5 indicates osteopenia, a T-score of 2.5 indicates osteoporosis, and a T-score of 2.5 indicates established or severe osteoporosis along with a history of fragility fractures.
For postmenopausal women and males over 50, WHO thresholds can be employed. A comparison of the patient's BMD with that of an age-matched population yields the Z-score.
A Z-score of 2 should trigger investigation for secondary osteoporosis causes.
 Think of conducting a secondary osteoporosis causes screening:
- Complete blood count, calcium, phosphorus, magnesium, total protein, albumin, liver enzymes, creatinine, and alkaline phosphatase in the serum together with 25-hydroxyvitamin D and parathyroid hormone.
- 24-hour urine salt, creatinine, and calcium to detect hypercalciuria
However, an anomaly (such as expanded intervertebral gaps, rib fractures, or vertebral compression fractures) should prompt assessment because plain radiographs lack the sensitivity to detect osteoporosis.

Tests in the Future & Special Considerations

Considering additional laboratory testing based on initial assessment, Zscore of 2.5 or less, or early age
hemochromatosis, iron, and ferritin
 Testosterone levels (in men, hypogonadism)
Multiple myeloma serum protein electrophoresis and free and light chains
 Free cortisol in urine (Cushing illness)
 Antibodies to tissue transglutaminase (celiac illness)
Other/Diagnostic Procedures Bone biopsy may be taken into consideration.

Interpretation of Tests
Reduced skeletal mass is visible in osteoporosis; trabecular bone has thinned or lost more than cortical bone

Management 
The following are requirements for patients who gain from osteoporosis treatment:
- T-scores of patients 2.5 without risk factors
- Postmenopausal women and men over 50 who have an osteoporotic vertebral/hip fracture or have BMD values that are consistent with osteoporosis (T-score 2.5) at the lumbar spine, femoral neck, or total hip region. - Postmenopausal women and men over 50 who have osteopenia (T-scores between 1.0 and 2.5) and a 10-year fracture risk of less than 20% or a risk of
- All men over the age of 50 who come with a hip or vertebral fracture or a T-score under 2.5 following an adequate evaluation; nonetheless, there is little research demonstrating that therapy is successful in men.
Treatment for osteopenia that focuses on reducing risk includes weight-bearing exercise, vitamin D supplementation (2,000 to 4,000 IU/day), decreasing alcohol consumption, and quitting smoking.

Treatment with 2,000–4,000 IU/day of vitamin D for all osteoporosis patients
Primary bisphosphonates:
Mechanism: Osteoclasts in skeletal tissue prevent bone resorption, lowering the frequency of both vertebral and nonvertebral fractures.
- Zoledronic acid 5 mg IV yearly or 5 mg IV every 18 months - Alendronate 10 mg PO daily or 70 mg PO weekly - Risedronate 5 mg PO daily, 35 mg PO weekly, or 150 mg PO monthly
Zoledronic acid (once every 18 months) reduced both vertebral (RR 0.46, 95% CI 0.28-0.74) and nonvertebral (HR 0.66, 95% CI 0.51-0.85) fractures when used as primary preventive.
Oral bisphosphonates are preferred for secondary osteoporosis prevention in mild-to-moderate cases.All bisphosphonates have comparable side effects, which include gastrointestinal issues such esophageal and stomach irritation.
Osteonecrosis of the jaw is a possibility, especially in cancer patients receiving IV therapy and large dosages of chemotherapy.
Patients who have been using bisphosphonates for more than five years may be at risk for developing atypical femur fractures.
Avoid taking oral bisphosphonates if you have:
- Inability to stand or sit erect for at least 30 to 60 minutes after taking the bisphosphonates. - Delayed esophageal emptying
- Hypocalcemia (correct before beginning treatment.)
- Severe renal impairment (CrCl 35 mL/min for alendronate and zoledronic acid and 30 mL/min for risedronate)

Next Line
Therapy using monoclonal antibodies
- 60 mg SC of denosumab every six months
 Blocking the human monoclonal antibody receptor activator of nuclear factor-B ligand (RANKL) receptor, which reduces bone resorption and osteoclast development.
 Can be thought of as a first treatment option for postmenopausal women who have a higher risk of fracture or who are ineligible for oral bisphosphonates. 
The drug of preference for people with renal insufficiency is denosumab.
Dermatologic reactions (dermatitis, eczema, rashes), musculoskeletal pain, hypocalcemia, osteonecrosis of the jaw, atypical femur fractures, and life-threatening infections (cellulitis and endocarditis) are only a few of the possible side effects.
Reevaluation is advised after five years of therapy; if low risk, therapy may be stopped. If the risk is still significant, treatment may be continued for up to 10 years.
Additionally, there may be an increased risk of rebound bone turnover after termination; consequently, it is advised to think about switching to an alternate or future bisphosphonate medication.
- Romosozumab 210 mg once a month (in two different injections).
 Sclerostin-inhibiting monoclonal antibody that promotes bone growth
For women with severe osteoporosis or who are at high risk for fractures, romosozumab therapy (12 months) is followed with alendronate. 
 May raise the possibility of unfavorable cardiovascular events, while mixing it with bisphosphonate therapy may lower the possibility.
PTH recombinant formulations (anabolic substances that activate osteoblasts to induce bone):
- Favored in people with severe osteoporosis because they can reduce fracture risk more quickly
20 mg SC of teriparatide each day
Studies have revealed a 65% decrease in the frequency of vertebral fractures and a 53% decrease in the frequency of nonvertebral fractures.
Despite being beneficial, usage is restricted to those at high risk for fractures (or those for whom earlier therapy proved failed).
After withdrawal, fractures and bone loss may develop quickly; as a result, sequential therapy with an antiresorptive drug (bisphosphonate) is advised.
 80 g SC of abaloparatide every day
 Teriparatide-like safety profile

Referral: a dental expert for oral inspections; endocrinology for recurring bone loss/fractures or unusual cases of osteoporosis


Additional therapies include physical therapy, fall prevention techniques, and weight-bearing exercise for 30 minutes three times each week.

Options for surgical procedures for people with compression fractures:
Vertebroplasty involves injecting orthopedic cement into the compressed vertebral body.
In kyphoplasty, cement is injected as a balloon is expanded inside the compressed vertebral body.

Admission Inpatient treatment for acute fracture pain

Drug holidays may be taken into consideration, along with continuous care and shared therapeutic decision-making with the patient.

Follow-up: Modifications to your way of life
Exercises that focus on balance and strength
 Enhancing calcium and vitamin D intake
DEXA analysis should be repeated.
Monitoring the patient.
Exercises that involve weight-bearing, such as stair climbing, jogging, and tai chi, have been demonstrated to lower the incidence of falls and fractures.
Repeat spinal imaging should be performed on patients who lose more than 2 cm in height. The majority of guidelines advise performing another DEXA scan to measure BMD two years after beginning bisphosphonate medication.
● After three to five years of treatment, conduct a risk assessment.
Consider ceasing treatment if the BMD T-score at the hip is less than 2.5 and there haven't been any hip or vertebral fractures. The patient may benefit from continuing treatment for an additional five years if BMD remains low or high risk for fractures.
Patients who have been taking bisphosphonates for five years (3 years on zoledronic acid IV) and have a stable BMD, no fractures in the past, and a low risk of fracture may be eligible for a pharmacological break.Patients who have been using bisphosphonates for five years who are at high risk for fracture (previous fragility fracture, advanced age, frailty, and high fall risk) should keep taking the medication; after six to ten years, a pharmacological break should be reconsidered.
Patients using bisphosphonates should be informed of the slight chance of developing jaw osteonecrosis, and dentist visits should be encouraged.


Maintain a healthy body weight through diet, and get enough calcium and vitamin D.

Prognosis 15% of vertebral and 20–40% of hip fractures may result in chronic care and/or premature death, however 80% of patients increase their bone mass, mobility, and pain tolerance with treatment.

Complications 
Recurrent fractures and excruciating, incapacitating agony