endocrine and kidney diseases - giustina

• The provided text is about Osteoporosis

Clinical Case: Marta

• Marta is a 66-year-old woman.
• She participates in sports occasionally, like skiing and swimming.
• Marta's diet is varied but low in dairy.
• She is a non-smoker and consumes social potus.
• She had one pregnancy and experienced spontaneous menopause at 52.
• She underwent hormone replacement therapy for a year before stopping.
• Marta has a history of arterial hypertension since age 56 and is on beta-blockers.
• She has gastroesophageal reflux disease.
• Her body weight is 55kg, height is 170cm, resulting in a BMI of 19.

Patient History

• Physiological history includes sports and diet.
• Pharmacological history includes beta-blockers
• There is no family history available
• Collecting family history from older subjects is challenging due to deceased relatives and unclear recollection of their medical issues.
• Obtaining a complete physiological history from older individuals can also be difficult, including the age of menarche.
• Menstrual life and estrogenized life are important in the context of a bone clinic.
• Shorter life with estrogens correlates with a higher risk of weaker bones.
• Details on the specific beta-blocker drug are not available.
• Various drugs, including glucocorticoids and omeprazole, can have a negative impact on bone health.
• Muscles exert a positive effect on bones when exercised regularly.
• Swimming is not ideal for bones due to the lack of muscle load.
• Skiing is not recommended for those with osteoporosis due to the increased risk of falls and fractures.
• Walking, especially in sunny conditions, is the recommended activity for individuals with osteoporosis.
• Social potus refers to drinking due to social influence.
• Reconstructing a patient's history may involve speaking to close relatives.
• A complete history includes physiological, pharmacological, family, and remote aspects with reason for referral.
• Physical examination includes weight and height, where thinness is a risk factor for osteoporosis.
• Marta's height and weight suggest a constitutional risk for weaker bones.
• The patient's interest in controlling her body shape may reflect her lifestyle.
• Marta's mother had a femur fracture at 70, and Marta wants to assess her own osteoporosis and fracture risk.
• She has not had recent blood chemistry or a MOC-DEXA examination.
• A complete physical examination is essential, as patient-reported information might be outdated.
• The accuracy of weight information might be more reliable than height in this case.
• Height measurements can be unreliable due to spine shortening and curving in older individuals with osteoporosis.
• Measuring blood pressure is important due to the patient's history of hypertension.
• Neuromuscular status and vertebral body pain should be evaluated.
• Back pain is a common reason for doctor referrals but should not be overlooked.
• Pain during movements like flexing could indicate an osteoporotic fracture at the vertebral level.

Arthrosis vs Osteoporosis

• Arthrosis is a degenerative joint problem, while osteoporosis is a metabolic problem.
• Arthrosis and osteoporosis can coexist, linked only by the risk factor of aging.
• Arthrosis does not directly cause fractures.
• Arthrosis typically affects small joints (fingers, hands, feet), but can involve large joints (vertebral bodies).
• Osteoporosis primarily affects large bones such as the femur, humerus, and vertebrae (thoracic and lumbar).
• Arthrosis is more common in the cervical vertebrae.

Bone Cells

• Bone cells include osteoblasts, osteoclasts, and osteocytes.
• Osteoclasts resorb bone through protein degradation and acidification stimulated by the RANK-RANKL pathway.
• Osteoblasts form new bone by synthesizing matrix proteins like collagen type 1 and osteocalcin, also responsible for bone mineralization.
• Both osteoclasts and osteoblasts have receptors for PTH, calcitonin, vitamin D, cytokines, and growth factors.
• Bone turnover is a dynamic process with simultaneous bone formation and resorption.
• PTH stimulates osteoblasts to express RANKL, which activates osteoclasts, leading to bone resorption.

Calcium Homeostasis

• Calcium regulation is essential for bone metabolism.
• Extracellular ionized calcium acts on calcium receptors or CaSR.
• In low blood calcium levels, parathyroid cells are stimulated, leading to PTH synthesis and release.
• PTH then increases blood calcium through renal tubular reabsorption.
• Bone needs to be metabolically active, with old bone being replaced to avoid a weaker skeleton.
• Osteoclasts and osteoblasts maintain a young and competent skeleton.
• Vitamin D is crucial for the mineralization phase, where new bone is mineralized. Vitamin D accounts for 80% of vitamin D in the blood.
• Vitamin D (cholecalciferol) needs hydroxylation in the liver (position 25) and kidney (position 1) to become active.
• PTH controls the final hydroxylation in the kidney, enhancing calcium reabsorption from the intestine.
• Estrogens regulate osteoclast activity.
• Non-estrogenized bodies, like menopausal women, have hyperactive osteoclasts, leading to increased bone resorption.
• The unbalance between osteoclast and osteoblast activity can cause osteoporosis.
• Vitamin D deficiency is common due to lack of sun exposure, affecting bone mineralization.

Osteoporosis Classification

• Distinguish between primary and secondary osteoporosis.
• Primary osteoporosis is post-menopausal, senile, or juvenile idiopathic.
• In a bone mass graph, the x-axis represents age, and the y-axis represents bone mass.
• Peak bone mass is higher in men compared to women.
• Women experience a significant fall in bone mass due to menopause.
• Peak bone mass is affected by genetics, nutrition, physical activity, and hormones.
• Osteoporosis is losing too much bone during menopause, increasing the risk of fracture.
• Men do not have an equivalent to menopause (andropause), leading to osteoporosis later in life.
• Hormonal replacement therapy can delay bone loss but is limited by its long-term oncological side effects.
• The bone mass threshold for defining osteoporosis is the same for men and women.

Secondary Osteoporosis

• Secondary osteoporosis is caused by factors beyond estrogen or testosterone loss.
• These factors are endocrine diseases, nutritional conditions, drugs, other conditions, and disorders of collagen.
• Endocrine diseases: hypogonadism, hyperthyroidism, Cushing's syndrome, acromegaly, hyperparathyroidism, growth hormone deficiency.
• Nutritional conditions: vitamin D/calcium deficiency, weight loss, malabsorption, gastric surgery, anorexia, malnutrition.
• Drugs: glucocorticoids, anti-epilepsy drugs, GnRH agonists, aromatase inhibitors, heparin, androgen deprivation therapy, PPIs.
• Other conditions: rheumatoid arthritis, inflammatory bowel disease.
• Hyperthyroidism: is catabolic, weakening bones.
• Cushing's Syndrome: increased bone loss, often caused by glucocorticoids.
• Vitamin D deficiency: from malabsorption, particularly celiac disease.
• Glucocorticoids: the main drugs leading to bone loss, used in vast diseases.
• They suppress immune system but are toxic to bones, especially with prolonged use.
• Rheumatoid arthritis: inflammation leading to bone loss.
• It can be caused by glucocorticoids
• Rheumatologists use glucocorticoids to reduce joint pain but must consider side effects.
• Consider all side effects of glucocorticoids, like gastric toxicity (use PPIs), and Cushing's syndrome.
• Always give the lowest effective dose of glucocorticoids.
• It can cause liver problems, and osteoporosis because the liver is where vitamin D is hydroxylated position 25.
• Rheumatologists should consider the risk of glucocorticoid-induced Cushing's syndrome.
• Biological treatments for rheumatoid arthritis are being researched to avoid glucocorticoid use.
• Glucocorticoids can induce dependence and side effects grouped under Cushing's syndrome.
• When starting pharmacological treatments, think about the interactions.
• PPIs given with glucocorticoids treat gastrointestinal damage but can also increase bone toxicity.
• Prostate cancer risk increases with prolonged testosterone exposure, while breast cancer risk increases with estrogen.
• Blocking testosterone or estrogens increases the risk of osteoporosis
• Blocking testosterone in men induces andropause, the biological correlate of the woman menopause.
• Tools used to control cancer can be toxic to other organs and cause side effects.
• Effective drugs used for HIV, cause metabolic syndromes with side effects
• Anti-androgen treatment for prostate cancer causes true andropause and increases osteoporosis risk.

Diagnosis of Osteoporosis

• Clinical evaluation: anamnesis, physical examination, and risk factor assessment.
• Imaging for diagnosis
• Laboratory tests

Clinical Evaluation

• Assess family and physiological history like fractures, menarche, pregnancy, and eating habits.
• Assess medical and recent medical history for diseases and drugs promoting secondary osteoporosis.

Risk Factors

• Modifiable: activity, calcium/vitamin D intake, BMI, alcohol, smoking, coffee.
• Unmodifiable: age, menopause, amenorrhea, corticosteroids, familiarity, genetics.
• Low BMI is modifiable, dietary with dairy is important.

Instrumental Diagnosis

• WHO defines osteoporosis by Bone Mineral Density - BMD via DEXA imaging
• BMD is the ratio of bone mineral content to the evaluated surface area
• T-score: BMD difference from healthy young adults
• Z-score: BMD difference from subjects of equal sex and age.

Threshold for Normality, Osteopenia and Osteoporosis

• T-score is used in post-menopausal women and men >50
• Normality: BMD more than -1 standard deviation from peak bone mass
• Osteopenia: BMD between -1 and -2.4 standard deviations
• Osteoporosis: BMD less than -2.5 standard deviations
• Severe Osteoporosis: BMD less than -2.5 + osteoporotic fracture

Fracture Sites

• Common sites of osteoporotic fracture are the wrist (Colle’s fracture), vertebral bodies and femur.
• Bone density measurement is lumbar vertebral bodies and femur
• Vertebral fractures are typical in women after menopause since 80% of bone metabolism is found in the vertebrae.
• Femoral density is important in ages >70.
• Vertebral fractures can be self-limiting and pain may be relieved with drugs.
• Spinal x-rays are important for heavy patients.

Therapeutic Approach

• Reduction of osteoporosis risk factors
• Dietary intake of calcium and Vitamin D
• Supplement with VitaminD and calcium supplements
• Manage calcium and Vitamin D deficiency with antiosteoporotic drugs

Calcium Requirement

• A normal calcium intake involves 1L of milk as an average
• Other alternatives include yogurt, cheese and mineral water

Vitamin D Requirement

• Need supplements to reach the desirable level, plus encourage a stimulating diary produce.

Anti-Osteoporotic Drugs

• Drugs that reduce activity on osteoclasts are Bisphosphonates and Denosumab
• Bisphosphonates: are pyrophosphates analogues that go directly in the osteoclasts and have a toxic effect on them.
• Denosumab: a monoclonal antibody acting against the pathway of RANK and RANK-L.
• Drugs that concerns a stimulation of osteoblasts: Teriparatide
• Teriparatide: an analogue of PTH.
• Intermittently parathyroid hormone is good for bones.