72. Histology | Bone Histology and Development

A 65-year-old postmenopausal woman presents with a history of multiple vertebral compression fractures. Her bone density scan shows markedly reduced bone mass. Loss of which hormone is the primary contributor to her condition?
A. Calcitonin
B. Parathyroid hormone
C. Growth hormone
D. Estrogen
E. Cortisol

D

• Estrogen (Correct): Estrogen inhibits osteoclast activity and cytokines (IL-1, IL-6, TNF, M-CSF) that promote bone resorption. Postmenopausal estrogen loss increases osteoclast-mediated resorption, leading to osteoporosis.

• A. Calcitonin: Lowers blood calcium but has a modest effect on bone density compared to estrogen loss.

• B. Parathyroid hormone: Increases osteoclast activity and blood calcium—elevated PTH causes osteitis fibrosa cystica, not postmenopausal bone loss.

• C. Growth hormone: Affects bone growth via osteoprogenitors but is not the cause of adult osteoporosis.

• E. Cortisol: Excess causes secondary osteoporosis, but not the classic postmenopausal type.

A 12-year-old boy presents with proportionate short stature. Laboratory tests reveal decreased growth hormone secretion. Which of the following best describes the underlying cause of his condition?
A. Impaired osteoclast resorption
B. Reduced stimulation of osteoprogenitor cells
C. Excess secretion of parathyroid hormone
D. Overproduction of estrogen before puberty
E. Failure of cartilage hypertrophy at the epiphyseal plate

B

• B. Reduced stimulation of osteoprogenitor cells (Correct): Growth hormone stimulates osteoprogenitor proliferation. GH deficiency reduces their activation, causing pituitary dwarfism (proportionate short stature).

• A. Impaired osteoclast resorption: Would cause osteopetrosis (dense but brittle bones).

• C. Excess PTH: Leads to hypercalcemia and bone resorption.

• D. Overproduction of estrogen: Causes early epiphyseal closure, not proportionate dwarfism.

• E. Failure of cartilage hypertrophy: Characteristic of achondroplasia, not GH deficiency.

A pathologist examines a biopsy of bone that shows dense, brittle tissue with obliterated marrow cavities leading to pancytopenia. Which of the following best explains the pathophysiology?
A. Excess osteoblast activity
B. Defective osteoclast function
C. Overproduction of osteoprotegerin
D. Hyperactive RANK-L signaling
E. Decreased hydroxyapatite deposition

B

• B. Defective osteoclast function (Correct): Seen in osteopetrosis—ineffective bone resorption leads to dense, brittle bone and loss of marrow space → pancytopenia.

• A. Excess osteoblast activity: Would increase bone formation, not cause marrow obliteration.

• C. Overproduction of OPG: Would inhibit osteoclast formation, possibly mimicking osteopetrosis, but primary defect is in the osteoclasts themselves.

• D. Hyperactive RANK-L: Causes increased osteoclast differentiation and bone loss (osteoporosis).

• E. Decreased hydroxyapatite: Causes osteomalacia, not dense bone.

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