Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
DISEASES OF BONE
Physiology of bone
Bone structure and metabolism
bone functions:
 providing support for the body
 protecting the hematopoietic system and the structures within the
cranium, pelvis, and thorax
 allowing for movement
 serving as a reservoir for calcium, phosphorus, magnesium, and
sodium
cortical (compact) bone - ~ 80% of the adult skeleton; shafts of the long
bones
trabecular (spongy, cancellous) bone - microscopically parallel lamellae;
predominates in the vertebral bodies, ribs, pelvis, and ends of the long
bones. It serves most of the metabolic functions
Calcium metabolism
total body calcium in normal adults ~ 1 to 2 kg; 99% is in the skeleton
physiologic roles of calcium; maintaining the structural integrity of the
skeleton and for cellular processes (it is also a intracellular second
messenger for many hormones, paracrine factors, and neurotransmitters).
extracellular calcium in plasma:
a) ionized calcium (~ 50%)
b) protein-bound calcium (~40%)
c) calcium that is complexed to bicarbonate, citrate, and phosphate etc.
(~ 10%)
acidosis decreases binding of calcium to albumin --> ionized calcium
increases; alkalosis produces the converse situation
intracellular calcium: ~ 1/10,000 of extracellular levels. This low
concentration is maintained by a system of active transport pumps
Calcium absorption: the average diet contains ~ 400 to 1,000 mg of
calcium a day, mostly derived from dairy products. 25 - 70% of the
ingested Ca are absorbed
the average daily Ca requirement is > 400 mg
1/21
Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
Ca absorption occurs principally in the duodenum and the jejunum by an
active process. The main determinant of intestinal absorption of calcium
is 1,25-(OH)2D.
Ca excretion: urine, feces, sweat; 7 - 10 g Ca are filtered by the
glomerulus each day, 98% of which is normally reabsorbed. The principal
sites of renal calcium reabsorption are the proximal tubule and the loop of
Henle. Reabsorption of renal tubular calcium is enhanced by PTH,
phosphate, metabolic alkalosis, thiazide diuretics, and increased
reabsorption of sodium.
Phosphorus metabolism
In the adult, phosphorus constitutes 10 to 13 g/kg of body weight; 80 85% is in the skeleton and 10% is intracellular.
Normal plasma inorganic phosphate (P) concentration is 0.8 to 1.4
mmol/l. P is 85% free and 15% protein bound.
P absorption is directly proportional to dietary P intake.
Most plasma phosphate is filtered by the glomerulus, after which 80 90% is actively reabsorbed. Urinary P excretion is increased by PTH,
phosphate loading, volume expansion, hypercalcemia, systemic acidosis,
hypokalemia, hypomagnesemia, glucocorticoids, calcitonin, thiazides,
and furosemide.
Causes of hypophosphatemia
Increased urinary losses
hyperparathyroidism
hypercalcemia of malignancy
oncogenic osteomalacia
extracellular fluid volume expansion
diabetes mellitus
acquired renal tubular defects (hypokalemia, hypomagnesemia)
X-linked vitamin D - resistant rickets
alcohol abuse
renal tubular acidosis
hypothyroidism
drugs: diuretics, glucocorticoids, calcitonin, bicarbonate
2/21
Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
Decreased intestinal absorption
vitamin D deficiency
malabsorption syndromes
antacid abuse
starvation
alcohol abuse
Shifts into cells
carbohydrate administration
acute alkalosis
nutritional recovery syndrome
acute gout
salicylate poisoning
G- bacteremia
posthypothermia
Consequences of severe hypophosphatemia
Acute
Hematologic
red cell dysfunction and hemolysis
leukocyte dysfunction
platelet dysfunction
Muscle
weakness
rhabdomyolysis
myocardial dysfunction
Kidney
increased 25-OH-D 1alpha-hydroxylase activity
increased calcium, bicarbonate, and magnesium excretion
metabolic acidosis
Reduced formation of 2,3-DPG with impaired tissue oxygen
delivery
CNS dysfunction
3/21
Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
Chronic
osteomalacia or rickets
Symptoms of hypophosphatemia usually do not occur until serum
inorganic phosphate levels fall below 0.32 mmol/l. CNS impairment
varies from irritability fatigue, and weakness to encephalopathy and
coma.
Th: milk is an excellent source of P, containing ~1000 mg/l. Sodium and
potassium phosphate tablets can be given. Intravenous P may be indicated
in rare circumstances.
Causes of hyperphosphatemia
Decreased renal phosphate excretion
renal failure (acute or chronic)
hypoparathyroidism
pseudohypoparathyroidism
acromegaly
etidronate
tumoral calcinosis
Increased phosphate entry into the extracellular fluid
excess phosphate administration
transcellular shifts
rhabdomyolysis
acute tumor lysis
hemolytic anemia
acidosis
catabolic states
infections
hyperthermia
fulminant hepatitis
vitamin D intoxication
In chronic renal insufficiency, normal serum P levels are maintained by
decreased renal P reabsorption until the GFR falls below 20 to 25 ml/min.
4/21
Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
The most important acute effects of hyperphosphatemia are hypocalcemia
and tetany. Hyperphosphatemia lowers serum calcium levels acutely by
complexing with calcium and chronically by inhibiting the activity of
renal 1alpha-hydroxylase, thereby diminishing synthesis of 1,25-(OH)2D.
This aggravates hypocalcemia both by impairing intestinal calcium
absorption and by inducing a state of skeletal resistance to the action of
PTH. Acute or chronic hyperphosphatemia can cause metastatic
calcifications.
Th: restricting dietary phosphorus, phosphate binders (aluminium
hydroxide, calcium carbonate).
Magnesium metabolism
In the adult, Mg constitutes ~ 0.35 g/kg of body weight. Slightly more
than half of total body Mg is in bone, and most of the remainder is
localized in the intracellular compartment. Mg is the second most
abundant intracellular cation, after potassium. ~ 60% of intracellular
magnesium is contained in the mitochondria, and only 5 to 10% is free in
the cytosol.
Mg metabolism bears some relationship to that of calcium:
 these cations compete for renal tubular reabsorption and may compete
for intestinal absorption;
 Mg and Ca are physiologic antagonists in the CNS;
 Mg is necessary for the release of PTH and for the action of the
hormone on the target tissues.
Normal plasma Mg concentration = 0.75 to 1.05 mmol/l.
The kidney is the main site of Mg excretion; ~ 2 to 10% of the filtered
load of Mg is normally excreted in the urine.
Hypomagnesemia
Mg deficiency usually occurs in association with more generalized
nutritional and metabolic abnormalities. It can be due to:
 decreased absorption,
 increased renal or intestinal losses or
 redistribution of Mg.
5/21
Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
Causes of hypomagnesemia
Decreased absorption
poor dietary intake
malabsorption syndromes
extensive bowel resection
ethanol effect on absorption
Increased gastrointestinal losses
acute and chronic diarrhea
intestinal and biliary fistulas
vomiting or nasogastric suction
Increased renal losses
chronic intravenous fluid therapy
chronic renal disease
osmotic diuresis
diabetes mellitus
hypercalcemia
phosphate depletion
metabolic acidosis
primary hyperaldosteronism
drugs
diuretics (furosemide)
aminoglycosides
cisplatin
cyclosporine
amphotericin B
ethanol
Internal redistribution
acute pancreatitis
"hungry bone syndrome"
The most common clinical presentations of hypomagnesemia are caused
by associated hypocalcemia (due to interference with the secretion and
action of PTH) and hypokalemia (due to an inability of the kidney to
6/21
Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
preserve potassium). Other clinical manifestations: neuromuscular
hyperexcitability, prolongation of the PR and QT intervals, arrhythmias.
Consequences of Mg deficiency
Neuromuscular
lethargy, weakness, fatigue, decreased mentation
neuromuscular irritability
Gastrointestinal
anorexia, nausea, vomiting
paralytic ileus
Cardiovascular
prolongation of PR and QT intervals
tachyarrhythmias
increased sensitivity to digitalis
Metabolic
hypocalcemia (due to decreased parathyroid hormone secretion and
action)
hypokalemia (due to renal potassium wasting)
Th: administer 2 g of MgSO4 every 8 hours i.m. or as an i.v. infusion.
Hypermagnesemia
almost always occurs in the setting of renal insufficiency. Neuromuscular
symptoms are the most common presenting problem of
hypermagnesemia.
Somnolence may be seen at concentrations of 3 mmol/l; the deep tendon
reflexes disappear at serum concentrations of 4 to 7 mmol/l; respiratory
depression and apnea occur at higher concentrations.
Th: in most cases, the only treatment needed is to discontinue Mg
administration. Dialysis in patients with renal failure. In emergencies 100
to 200 mg calcium i.v.
Vitamin D
it is more properly a steroid hormone than a vitamin. Recommended daily
intake for adults is 400 IU. In the target cell, 1,25-(OH)2D binds to
specific, high-affinity receptor in either the cytoplasm or the nucleus. The
7/21
Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
DNA-binding domain of the hormone-receptor complex then interacts
with the hormone-responsive element in the genome, producing either upor downregulation of the gene in question.
Function of vitamin D
Vitamin D acts with PTH to maintain the level of ionised calcium in
extracellular fluid by actions on the intestine, bone, and, to a lesser extent,
the kidney. Vitamin D enhances the intestinal absorption of calcium and
phosphate and enhances the mineralization of osteoid. It increases bone
resorption.
Diagnosis of vitamin D deficiency: low serum levels of 25-OH-D. Other
findings:
mild
hypocalcemia,
hypophosphatemia,
secondary
hyperparathyroidism, low levels of urinary Ca excretion.
Hypervitaminosis D
occurs from the excessive ingestion of vitamin D or from the abnormal
conversion in diseases such as sarcoidosis, TBC, or certain T cell
lymphomas.
Clin: hypercalcemia and metastatic calcifications. The hypercalcemia is
due not only to vitamin D's effect on calcium absorption but also to its
osteolytic effects.
Calcitonin
is a 32-amino acid peptide secreted by the parafollicular C cells of the
thyroid gland. The main biologic effect is to inhibit osteoclastic bone
resorption.
Hypocalcitoninemia
patients with calcitonine deficiency do not have any recognizable
abnormalities.
Hypercalcitoninemia
is seen in medullary carcinoma of the thyroid gland. These patients do not
have any associated bone disease or metabolic disorders of calcium or
inorganic phosphate.
8/21
Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
The parathyroid glands
Parathormone (PTH) is an 84 amino acid single-chain polypeptide with a
molecular weight of 9,500. The biologic activity of PTH resides in the
first 34 residues. PTH secretion is controlled primarily by the serum
ionized calcium level: when the level falls, PTH secretion is stimulated;
when it rises, the secretion of PTH is suppressed. With prolonged
hypocalcemia, the parathyroid glands can become markedly hyperplastic.
Actions of parathyroid hormone
The main function of PTH is to defend against hypocalcemia by:
 stimulation of bone resorption by osteoclasts;
 stimulation of renal tubular reabsorption of calcium and, magnesium;
 inhibition of the renal tubular reabsorption of phosphate and
bicarbonate;
 stimulation of synthesis of the active form of vitamin D by activating
the 1alpha-hydroxylase in the kidney.
Hypercalcemia
causes: hyperparathyroidism, malignancy
Signs and symptoms of primary hyperparathyroidism
Related to hypercalcemia
central nervous system
lethargy
drowsiness
depression
impaired ability to concentrate
confusion
stupor
coma
Neuromuscular
proximal muscle weakness
hyporeflexia
9/21
Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
Gastrointestinal
nausea, vomiting
anorexia
constipation
peptic ulcer disease
pancreatitis
Renal
polyuria
polydipsia
decreased concentrating ability
impaired renal function
nephrocalcinosis
nephrolithiasis
Cardiovascular
hypertension
short QT interval
bradycardia
increased sensitivity to digitalis
Related to hypercalciuria
nephrolithiasis
Related to PTH effect on bone and joints
arthralgias
bone pain
bone cysts
gout
pseudogout
The peak incidence of primary hyperparathyroidism occurs in the 20s to
40s, and it is more common in women than in men.
Etiology
Parathyroid adenoma is seen in ~85% of cases. Most of the remaining
15% have hyperplasia of all four glands, although the enlargement is
often asymmetric.
10/21
Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
Hyperparathyroidism may occur as part of multiple endocrine neoplasia
(MEN) type I (hyperparathyroidism, pancreatic islet cell tumors, and
anterior pituitary tumors) or MEN type II (hyperparathyroidism,
medullary carcinoma of the thyroid, and pheochromocytoma).
Familial hyperparathyroidism - patients have parathyroid hyperplasia
inherited in an autosomal dominant fashion.
Parathyroid carcinoma occurs rarely in patients
hyperparathyroidism and tends to grow slowly.
with
primary
Symptoms and signs
Most patients with primary hyperparathyroidism are asymptomatic at
presentation or present with vague symptoms. 10 - 15% develop kidney
stones composed of calcium oxalate or calcium phosphate.
Lab: serum Ca levels are continuously or intermittently elevated and
serum phosphorus levels tend to be low. ALP may be elevated, esp. in
patients with osteitis fibrosa cystica. Urinary calcium levels may be
normal or elevated. Serum PTH levels are elevated in most patients.
X-ray: most patients show no radiographic evidence of bone disease.
Osteopenia may be seen. Bone densitometry may show a disproportionate
loss of cortical bone. Nephrocalcinosis or renal stones may be seen.
Indications for surgical treatment of patients with asymptomatic primary
hyperparathyroidism
 a markedly elevated serum calcium level
 a history of prior life-threatening hypercalcemia
 kidney stone
 creatinine clearance reduced by > 30%
 hypercalciuria > 100 mmol/24 hr
 bone density more than 2 standard deviations below controls
 patient characteristics:
patient requests surgery
consistent follow-up is deemed unlikely
coexistent illness complicates medical management
patient is < 50 years old
If medical surveillance is recommended:
patients should be seen on a regular basis
11/21
Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
adequate hydration should be maintained
thiazide diuretics should be avoided
oral phosphate administration may be beneficial if
hypophosphatemia is present
in postmenopausal women, estrogen replacement therapy may
lower serum calcium levels
progression of symptoms requires surgery
Hypercalcemia of malignancy
occurs in 10 - 20% of cancer patients, usually late in the course of
malignancy, and survival is often very short.
Localized bone destruction is often an important cause of hypercalcemia.
Tumor metastases may release bone-resorbing cytokines directly into the
skeleton or may stimulate host mononuclear cells to elaborate mediators,
which stimulate nearby osteoclasts to resorb bone. Myeloma cells secrete
TNF-alpha and -beta and interleukin-1 and -6 etc.
Humoral hypercalcemia of malignancy. In many patients with
malignancy-associated hypercalcemia, the primary mechanism is
increased osteoclastic bone resorption caused by production of a PTH
related peptide (PTHrP). It is a 141 amino acid protein in which 9 of the
first 13 AA are identical to PTH. Immunoassays for PTH do not detect
PTHrP.
Treatment of hypercalcemia
should be directed toward reversing the underlying abnormality. In severe
hypercalcemia (> 3.3 mmol/l):
 hydration with isotonic saline
 furosemide
 glucocorticoids (prednisone 50 to 100 mg/day)
 calcitonin (2 to 4 IU/kg every 6 to 12 hours sc or im)
 mithramycin 15 to 25 µg/kg by infusion over 2 to 4 hours
 phosphate may be given in the presence of hypophosphatemia and
good renal functions per os
 biphosphonates (etidronate, pamidronate) - structural analogues of
pyrophosphate that inhibit osteoclast-mediated bone resorption.
 dialysis may be required in acute hypercalcemia and renal
insufficiency
12/21
Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
Hypocalcemia
In hypoparathyroidism, there is reduced mobilisation of calcium from
bone, reduced renal reabsorption of calcium, reduced renal clearance of
inorganic phosphate, and decreased intestinal calcium absorption due to
reduced synthesis of 1,25-(OH)2D. The results are hypocalcemia and
hyperphosphatemia.
Causes of hypocalcemia
hypoparathyroidism
idiopathic
autoimmune destruction
postsurgical
hypomagnesemia
post-neck irradiation
infiltrative, eg. granulomatous disease
DiGeorge's syndrome (absence of the parathyroid glands and the
thymus with severe immunodeficiency)
parathyroid hormone resistance
pseudohypoparathyroidism
hypomagnesemia
vitamin D deficiency
decreased dietary intake
lack of sunlight exposure
intestinal malabsorption
postgastrectomy
anticonvulsant therapy
vitamin D-dependent rickets type I
vitamin D resistance
vitamin D-dependent rickets type II
chronic renal failure
hyperphosphatemia
renal failure
tumor lysis
13/21
Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
rhabdomyolysis
excessive phosphate administration
hungry bone syndrome
osteoblastic metastases (e.g., prostate)
acute pancreatitis
multiple citrated blood transfusions
G- sepsis
antiresorptive agents (biphosphonates, calcitonin)
Signs and symptoms of hypocalcemia
Neuromuscular irritability
paresthesias
carpal pedal spasm
laryngospasm
bronchospasm
blepharospasm
tetany
CNS
seizures
EEG abnormalities
increased intracranial pressure with papilledema
extrapyramidal disturbances
Cardiovascular
prolonged QT interval
heart block
congestive heart failure
Other
abnormalities of teeth, fingernails, skin, and hair
lenticular cataracts
Lab: hypoparathyroidism is characterised by hypocalcemia,
hyperphosphatemia, low PTH levels. In chronic renal failure, there is
secondary hyperparathyroidism and hyperphosphatemia.
14/21
Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
Th: acute symptomatic hypocalcemia - calcium salt infusions i.v.
chronic hypocalcemia: oral calcium + vitamin D. In hypoparathyroidism,
high doses of vitamin D2 (e.g. 25,000 to 100,000 IU/day) plus oral
calcium are required. If patients are hyperphosphatemic, administering
aluminum-containing antacids may be necessary. Hypercalciuria can be
controlled by thiazide diuretics. In patients with chronic renal failure,
hyperphosphatemia should be controlled with oral calcium supplements
alone to avoid metabolic bone disease from aluminum toxicity.
Differential diagnosis of hypercalcemia
primary hyperparathyroidism
malignant disease
osteolytic metastases (breast, myeloma)
humoral hypercalcemia of malignancy (lung, head, neck,
esophagus, renal cell, ovary)
hematologic malignancies (lymphoma, leukemia)
sarcoidosis, tuberculosis
thyrotoxicosis
drug-induced
vitamin D intoxication
vitamin A intoxication
thiazide diuretics
lithium
tamoxifen
immobilization (in setting of high bone turnover)
milk-alkali syndrome
familial hypocalciuric hypercalcemia
adrenal insufficiency
acute and chronic renal failure
pheochromocytoma
Osteomalacia and rickets
Osteomalacia is a failure to mineralize the newly formed osteoid
normally. In rickets, there is also an abnormality in the zone of
15/21
Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
provisional calcification related to enchondral skeletal growth at the open
epiphyses.
Pathogenesis
Optimal mineralization requires:
 an adequate supply of calcium and phosphate ions from the
extracellular fluid;
 appropriate pH (~ 7.6);
 normal bone matrix;
 control of inhibitors of mineralization.
Causes of osteomalacia and/or rickets
A. Vitamin D deficiency
decreased formation of vitamin D or metabolites
decreased action of 1,25-(OH)2D
increased metabolism or excretion of vitamin D (isoniazid,
rifampin, nephrotic syndrome, CAPD)
B. Chronic phosphate depletion
alcohol abuse
vitamin D deficiency
aluminum hydroxide overdosage
selective renal tubular leaks
Fanconi's syndrome
X-linked vitamin D-resistant rickets and adult-onset VDRR
oncogenic osteomalacia
C. Systemic acidosis
distal renal tubular acidosis
proximal renal tubular acidosis
ureterosigmoidostomy
Fanconi's syndrome
D. Calcium malabsorption and chronic hypocalcemia
E. Inhibitors of mineralization
sodium fluoride
disodium etidronate
16/21
Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
aluminum
systemic acidosis
Clinical manifestations of rickets and osteomalacia
Rickets: skeletal pain and deformity, fracture of the abnormal bone,
disturbances in growth. Dental eruption is delayed and enamel defects are
common. If treated appropriately before age 4, the skeletal deformities
are usually reversible.
Osteomalacia: diffuse skeletal pain, proximal muscle weakness, bone
tenderness, and hypotonia with preservation of brisk reflexes
Lab: slight hypocalcemia, hypophosphatemia, elevated ALP, low-normal
urinary calcium excretion, elevated level of PTH. Serum levels of 25-OHD are often depressed.
X-ray: diffuse osteopenia; the only specific finding is the pseudofracture
(Looser's zone).
In rickets, the epiphyseal growth plate is widened leading to flaring,
cupping, and fraying of the metaphyses. Bowing of long bones, scoliosis,
a bell-shaped thorax, basilar invagination of the skull, and acetabular
protrusion may occur.
Dg: osteomalacia - iliac crest bone biopsy
rickets - clinical and radiographic findings
Th: calcium + vitamin D, in some patients also phosphate. Normalization
of serum ALP and PTH levels may take several months.
Osteoporosis
= parallel reduction in bone mineral and bone matrix. During the course
of their lifetime, women lose ~ 50% of their trabecular bone and 30% of
their cortical bone, and 30% of all postmenopausal women eventually
will have osteoporotic fractures. By extreme old age, one third of all
women and one sixth of all men will have a hip fracture.
Pathogenesis: bone density depends on both the peak density achieved
during development and the subsequent adult bone loss.
Factors affecting peak bone density:
gender
race
genetic factors
17/21
Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
gonadal steroids
growth hormone
timing of puberty
calcium intake
exercise
Men have higher bone density than women. Both men and women with
constitutionally delayed puberty have decreased peak bone density.
Physiologic causes of adult bone loss
After peak bone density is reached, it remains stable for years and then
declines. Bone loss begins before menopause in women and in the 20s to
40s in men. During the first 5 to 10 years of the menopause, trabecular
bone is lost faster than cortical bone, with rates of ~ 2 to 4% and 1 to 2%
per year, respectively. A woman can lose 10 to 15% of her cortical bone
and 25 to 30% of her trabecular bone during this time, a loss that can be
prevented by estrogen replacement therapy.
Rates of bone loss vary considerably among women. A subset of women
in whom osteopenia is more severe than expected for their age are said to
have type I ("postmenopausal") osteoporosis. This often presents with
vertebral "crush" fractures or Colles' fractures.
Estrogen deficiency may increase local production of bone-resorbing
cytokines such as IL-1, IL-6 and TNF. Estrogen deficiency increases the
skeleton's sensitivity to the resorptive effects of PTH.
Once the period of rapid postmenopausal bone loss ends, bone loss
continues at a more gradual rate throughout life. The osteopenia that
results from normal ageing, which occurs in both women and men, is type
II or "senile" osteoporosis. Fractures of the hip, pelvis, wrist, proximal
humerus, proximal tibia, and vertebral bodies are common.
Secondary causes of osteoporosis
Endocrine disease
female hypogonadism
hyperprolactinemia
hypothalamic amenorrhea
anorexia nervosa
premature and primary ovarian failure
18/21
Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
male hypogonadism
primary gonadal failure (Klinefelter's syndrome)
secondary gonadal failure
delayed puberty
hyperthyroidism
hyperparathyroidism
hypercortisolism
growth hormone deficiency
Gastrointestinal diseases
subtotal gastrectomy
malabsorption syndromes
chronic obstructive jaundice
primary biliary cirrhosis and other cirrhoses
lactase deficiency
Bone marrow disorders
multiple myeloma
lymphoma
leukemia
hemolytic anemias
systemic mastocytosis
disseminated carcinoma
Connective tissue diseases
osteogenesis imperfecta
Ehlers-Danlos syndrome
Marfan's syndrome
homocystinuria
Drugs
alcohol
heparin
glucocorticoids
thyroxine
anticonvulsants
19/21
Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
cyclosporine
gonadotropin-releasing hormone agonists
chemotherapy
Miscellaneous
immobilization
rheumatoid arthritis
Clinical manifestations
Osteoporosis is asymptomatic unless it results in a fracture (vertebral
compression fracture, or wrist, hip, ribs, pelvis, humerus). Back pain
usually begins acutely.
Radiographic findings: loss of trabecular bone in the vertebral bodies,
vertebral deformity - collapse, anterior wedging, Schmorl's nodules.
Dg: measuring bone mineral density.
Techniques: quantitative computed tomography of the spine, singlephoton absorptiometry of the proximal forearm, dual-photon
absorptiometry of spine and hips; dual-energy X-ray absorptiometry
(DXA) of the lumbar spine or hip is the method of choice.
Treatment
At present, it is not possible to reverse established osteoporosis. Early
intervention can prevent osteoporosis in most people, and later
intervention can halt the progression.
Physical therapy, corset, exercise.
Calcium can retard cortical bone loss in menopause. Postmenopausal
women should consume 1,000 to 1,500 mg/day of calcium.
Estrogen replacement therapy prevents bone loss in estrogen-deficient
women. The minimally effective doses are 0.625 mg/day of conjugated
estrogens, 2 mg/day of estradiol and 25 µg/day of ethinyl estradiol.
Calcitonin prevents spinal bone loss both in early and late
postmenopausal women. The recommended dose is 200 IU intranasally
each day, given with adequate calcium and vitamin D. It also has a
significant analgesic effect.
Biphosphonates inhibit osteoclastic bone resorption. They increase spinal
bone mineral density and decrease the incidence of vertebral fractures in
late postmenopausal women when given for 2 to 3 years. The commonly
20/21
Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
used dose of etidronate is 400 mg/day for the first 2 weeks of every 3month period. Alendronate is 50 times as potent as etidronate. The
recommended dose is 10 mg daily.
Vitamin D - deficiency in the elderly is common. Small doses (800
IU/day) plus calcium dramatically reduce the incidence of hip and other
fractures in elderly women. This therapy can be recommended to
virtually all postmenopausal women.
Future therapies: antiestrogens tamoxifen and raloxifene; sodium
fluoride; PTH.
Glucocorticoid-induced bone loss
Glucocorticoids suppress osteoblast activity and a vitamin D-independent
intestinal calcium absorption. The predominant effect is a loss of
trabecular bone. Calcitonin or cyclic etidronate can prevent spinal bone
loss in patients receiving long-term glucocorticoid therapy. Physiologic
vitamin D replacement (400 IU/day) can be safely recommended in all
patients receiving glucocorticoids and calcium supplementation (1000
mg/day) should be added unless urinary calcium excretion is excessive.
-----------------------
21/21