Music Exam 1

Describe bone mineral density

Describe bone mineral density

How much bone is in the matrix, diagnostic tool for osteoporosis and osteopenia. Biggest predictor of a fracture.

How is bone density regulated?

Osteoblasts build up bone using calcium in the blood, osteoclasts resorb bone which releases calcium into the blood

What hormones affect calcium homeostasis?

Parathyroid hormone (PTH) increases blood calcium levels through increased bone resorption. Calcitonin inhibits osteoclast activity, decreasing bone resorption and decreasing blood calcium levels. Vitamin D increases calcium absorption in the intestines.

How is bone loss monitored?

BMD scans, report as either a t-score (standard deviation compared to a healthy 30 year old) or a z-score (standard deviation compared to the same age and gender)

Define osteoporosis

Systemic disease characterized by low bone mass and microarchitecture deterioration with consequent increase in bone fragility and susceptibility to fracture

Osteoporosis diagnosis

T-score <2.5, severe bone mineral density loss

Osteoporosis risk factors

increased age

caucasian or asian

thin body frame

early menopause (<45)

late menarche (>16)

family history

diet lacking vitamin D and calcium

sedentary lifestyle

type 1 diabetes

cigarette smoking

heavy alcohol use

Secondary causes of osteoporosis

corticosteroid use/cushing’s syndrome

renal failure

hyperparathyroidism

hyperthyroidism

paget’s disease

GI dysfunction

rheumatoid arthritis

eating disorders

vitamin D/calcium deficiency

hypogonadism

Remember the chicken

Chickens on a calcium free diet still produced hard shelled eggs, but their skeletons were extremely weak. Shows the skeleton isn’t static and is the largest source of calcium in the body.

How is bone mineral density measured?

Dual energy X-ray absorptiometry (DEXA) scan, expressed as mineralized tissue in an area scanned

Why is measuring BMD important?

single most important predictor of future fractures

How are BMD and risk of future fractures related?

Inverse relationship (decrease in BMD, increase in risk of future fracture)

What is a t-score and what does it represent?

Bone mineral density compared to a “young healthy adult” (30 year old), reported as the difference in standard deviation from a mean

Normal t-score

(-)1 - +1

Low bone mass t-score (osteopenia)

1-2.5 STD below mean

osteoporosis t-score

More than 2.5 std below mean

severe osteoporosis defintion

t-score greater than 2.5 std below the mean and 3+ osteoporotic fractures

Normal z-score

0-2 standard deviations below average

Low z-score

Greater than 2 stds below mean

What is the most reliable and best predictor of future fractures

Hip BMD

Weaknesses of BMD

static, no insight into bone turnover

Organ systems that regulate blood calcium levels

GI, skeletal, renal

Which system is the major pathway of blood calcium regulation?

skeletal system

osteocytes

mature bone cells in the matrix, compose a vast majority of bone cells, many functions

osteoblasts (OBs)

bone forming cells that facilitate mineralization of calcium, phosphate, and hydroxyapatite. promotes bone matrix

osteoclasts (OCs)

bone degrading cells, promote resorption of bone, promote bone remodeling

In what ways does the skeleton adapt?

size, shape, integrity to promote mineral homeostasis

salubrious (healthy) bone remodeling

growth, repair of damage, response to mechanical stress

What does calcitonin do?

inhibit OC activity, inhibits bone resorption, promotes hypocalcemia

Vitamin D’s role

increase calcium absorption in intestines

What does PTH do?

increase blood calcium levels by stimulating calcium resorption from bones, calcium reabsorption in the kidneys, and vitamin D synthesis

Age of peak bone mass

30

Why do we care about preventing fractures?

people that have severe fractures (hip, vertebrae) have a greater chance of mortality and only 50% of hip fracture pts regain the same level of independence

Why does renal failure cause osteoporosis?

failure to activate vitamin D

Why is hyperparathyroidism a cause of osteoporosis?

increases PTH levels, increasing OC activity, increasing bone resorption

What is the #1 cause of osteopenia/osteoporosis?

glucocorticoid use

Drugs that are linked to osteopenia/osteoporosis

glucocorticoids, anticonvulsants, lithium, chronic use of phosphate-binding agents, methotrexate, loop diuretics, excess thyroid supplementation

ways to prevent bone loss

adequate calcium and vitamin D intake, smoking cessation, limiting alcohol intake, weight bearing exercise, avoid falling

Goal of osteoporosis treatment

prevent or slow existing bone loss and build up existing bone, reduce the risk of fracture

Antiresorptive agents

bisphosphonates, calcitonin, denosumab, estrogen, SERMs, testosterone

Anabolic agents

teriparatide, abaloparatide, romosozumab

General daily adult dose of calcium

1 gram per day

Daily dose of calcium for men >70 and women >50

1.2 grams per day

Best salt form of calcium for absorption

phosphate

Calcium salt form that doesn’t require acid

citrate, lactate

What must be given to patients when they’re being treated for osteoporosis?

calcium and vitamin D supplements

Bisphosphonates MOA

bind to sites of active resorption on bone, inhibit osteoclast activity, inhibit further bone resorption

Frequency of alendronate

weekly

risedronate dosing frequency

weekly or monthly

ibandronate dosing frequency

monthly

zoledronate dosing frequency

yearly

Instructions for taking bisphosphonates

take on an empty stomach, full glass of water, take 30 min prior to food, do not lay down after taking

duration of bisphosphonate use

10 years for high risk patients, 5 years on then 5 years off repeating if needed

Calcitonin MOA

inhibit OCs to decrease bone resorption

Why do we use salmon calcitonin?

longer acting and more potent

Is calcitonin generally a first line agent?

no

Estrogen supplement MOA

directly inhibit OCs, stimulate OBs, antagonize PTH

SERM activity sites

estrogen agonist at bone, estrogen antagonist everywhere else

Major adverse effects of estrogen and SERMs

blood clots, uterine cancer, breast cancer

Denosumab MOA

mAB that prevents the activation of OCs, increasing bone mass and strength

Denosumab indications

postmenopausal women with OP at high risk for fractures, patients who failed other treatments, chemotherapy-induced bone loss

When do we use anabolic therapy?

When patients are at the highest risk for OP fractures and have failed other therapies

teriparatide MOA

paradoxical, binds PTH1R receptor and stimulates OB activity when given in a cyclic and pulsed manner

Duration of teriparatide therapy

2 years, then generally follow up with an anti-resorptive med

abaloparatide compared to teriparatide

same for everything except for the cost

Who is most commonly diagnosed with osteoporosis?

post menopausal women

What is osteoporosis?

Bone disorder with decreased bone density, impaired bone structure, and bone strength

What does osteoporotic bone look like?

Spongy

Non-modifiable risk factors

female, age >65, asian or white ethnicity, dementia, family history, poor health or fragility, early menopause

potentially modifiable risk factors

alcohol use, tobacco use, caffeine intake, calcium intake, exercise, body weight, medication use

medications that increase fracture risk

anticoagulants, anticonvulsants, aromatase inhibitors, chemotherapy drugs, glucocorticoids, GnRH agonists, immunosuppressants, loop diuretics, progestins, PPIs, SSRis, SGLT-2 inhibitors, TZDs, thyroid products

osteoporotic risk factors MnEmOnIc

lOw calcium intake

Seizure meds

Thin build

Ethanol intake

hypOgonadism

Previous fracture

thyrOid excess

Race asian or white

Steroid use

Inactivity

Smoking

When is the fracture risk assessment (FRAX) used

all post menopausal women, men >50 years old

Who should have BMD testing?

women >65, women 50-64 if FRAX >9.3%, men >70, post menopausal women and men >50 with risk factors, adults with a fracture after age 50, adults taking meds known to increase bone loss or fracture risk

When is vertebral imaging indicated?

women >70, men >80, women >65 if t-score <1.0, loss of height >4cm, glucocorticoid therapy equivalent to >5mg of prednisone per day for >3 months

Gold Standard test for BMD

DEXA scan

FRAX score

Predicts 10 year probability of hip fracture and major osteoporotic fracture

Bone turnover markers (BTM)

Serum tests that reflect either bone resorption or formation, not for diagnosis but assesses skeletal activity and shows if therapy is responsive

osteoporosis diagnosis

one of the following:

• t-score <-2.5

• low-trauma spine or hip fracture regardless of BMD

  • osteopenia with fragility fracture

• osteopenia and high FRAX probability

Non-pharm osteoporosis treatment

adequate calcium and vitamin D intake, exercise (weight-bearing, resistance, balance), avoid tobacco, limit alcohol intake, reduce fall risk

ways to prevent falls

anchor rugs, minimize clutter, remove loose wires, nonskid mats, handrails, lights, sturdy and low heeled shoes

How much calcium is in a product based on the food label?

Label lists % of daily value of 1000 mg

How much calcium is in this?

300 mg (1000mg*0.30)

Is diet generally adequate for calcium intake?

No, need 1000-1200 mg of calcium per day

calcium carbonate

• 40% elemental calcium

• needs acid

• take with meals

  • side effects: constipation and kidney stones

calcium citrate

• 21% elemental calcium

• doesn’t need acid for absorption

• don’t need to take with meals

  • side effects: constipation, kidney stones

normal daily dose of vitamin D

20-50 ng/mL

When is treatment strongly recommended for osteoporosis?

• osteopenia with a history of fragility fracture of the hip or spine

• t-score < -2.5 in the spine, femoral neck, total hip, of 1/3 radius of the hip

  • t-score between -1.0 and -2.5 if the FRAX score is >20% for major osteoporotic fracture of >3% for hip fracture

First line OP therapy for high risk patients with no prior fractures

alendronate, denosumab, risedronate, zoledronate

First line OP therapy for very high risk patients and those who have prior fractures

abaloparatide, denosumab, romosozumab, teriparatide, zoledronate

Bisphosphonate examples

alendronate, ibandronate, risedronate, zoledronic acid

What is first line therapy for treatment and prevention of OP?

bisphosphonates

Bisphosphonate MOA

increases bone density by inhibiting OC activity and bone resorption, reduces vertebral fracture risk

Which bisphosphonates do we avoid using in CrCl <35?

alendronate and zoledronic acid

Which bisphosphonates do we avoid using in CrCl <30?

all (alendronate, zoledronic acid, ibandronate, risedronate)

Contraindications for bisphosphonates

• inability to sit upright/stand for at least 30 min (60 min with ibandronate)

• esophageal abnormalities

• difficulty swallowing

• hypocalcemia (can correct before use)

Bisphosphonates warnings

osteonecrosis of jaw, atypical femur fractures, esophagitis, renal impairment

Bisphosphonates counseling points

• administer on an empty stomach

• take with 6-8 oz of water

• do not eat for at least 30 min

  • remain upright for 30 min (60 min for ibandronate)

Raloxifene MOA

SERM, estrogen agonist at bone, estrogen antagonist at breast and uterus

Raloxifene dose

60 mg PO qD