Metabolic Bone Disease — Rickets, Osteomalacia, Paget Disease and Hyperparathyroidism on X-ray

Bone is continually remodelled: osteoclasts resorb it and osteoblasts lay down the osteoid matrix, on which hydroxyapatite mineral is deposited. Hormones, chiefly parathyroid hormone (PTH) and calcitonin acting on serum calcium, steer this process. A metabolic bone disease is any disorder in which this balance fails because of a mineral, vitamin D, hormonal or turnover abnormality. For exams the useful split is by the defect.

Osteomalacia means 'bone softening' in adults, usually due to prolonged vitamin D deficiency causing abnormal osteoid mineralisation. Rickets, in contrast, is deficient mineralisation at the cartilage of the growth plates in children, and occurs only before the epiphyses fuse. The two often coexist in children. Full coverage of the childhood disease is on the rickets page; see also vitamin deficiencies.

• Rickets, earliest change: radiolucent lines at the epiphysis–metaphysis junction and widening of the epiphyseal plate from accumulated non-mineralised osteoid.
• Rickets, established: cupping, splaying, fraying and trabecular change of the metaphysis; delayed or small epiphyseal centres; thin, osteopenic cortex; rachitic rosary and widened costochondral junctions on chest films; bowing and pathological fractures in advanced disease.
• Osteomalacia: Looser zones (pseudofractures) are the classic sign: transverse lucencies perpendicular to the cortex, typically bilateral and symmetrical at the femoral necks, shafts and pubic and ischial rami; decreased distinctness of vertebral trabeculae; low bone density.
• Biochemistry: typically hypophosphataemia, hypocalcaemia or both, with raised alkaline phosphatase; PTH rises and urinary calcium falls as early markers of calcium deprivation.

Treatment corrects the cause and the deficiency. StatPearls gives, for severe vitamin D deficiency, 50,000 IU of ergocalciferol or cholecalciferol weekly for 8 to 12 weeks, then 800 to 2,000 IU of vitamin D3 daily for maintenance, with serum and urine calcium monitored. In rickets, single large 'stoss' doses of 100,000 to 600,000 IU are an option in infants over 1 month when compliance is poor, orally preferred. Compare with renal tubular acidosis.

Paget disease is a focal skeletal disorder of abnormal bone remodelling: excessive osteoclastic resorption is followed by compensatory osteoblastic activity, producing disorganised bone that is less compact, mechanically weaker, highly vascular and prone to fracture. It is the second most common metabolic bone disorder in older adults after osteoporosis; over 75% of patients are asymptomatic, it is usually seen after the age of 50, and it is rare in Asia and Africa. The axial skeleton (spine, pelvis, skull) is most often affected, and one bone alone is involved in about a third.

• Stages: osteolytic, mixed, then osteosclerotic; a final stage may involve malignant change.
• Histology: giant multinucleated osteoclasts and irregular bone fragments resembling jigsaw puzzle pieces, the histological hallmark; marrow replaced by vascular fibrous tissue.
• X-ray: cortical and trabecular thickening, bone expansion, osteosclerosis and osteolytic areas; cotton-wool skull (patchy areas of increased density).
• Labs: raised alkaline phosphatase, serum calcium and phosphate normal; markers of resorption (N-telopeptide, urinary hydroxyproline) and formation (P1NP) are raised; hyperuricaemia is common.
• Bone scan: shows the extent and monitors response; may detect lesions before symptoms.

Complications: bone pain and deformity, incomplete fractures (tibia, femur; subtrochanteric femoral fractures), hearing loss from petrous temporal involvement, cranial nerve compression, basilar invagination, spinal cord compression, secondary osteoarthritis and high-output cardiac failure from hypervascularity. Osteosarcoma in pagetic bone is rare but fatal and should be suspected when swelling or pain suddenly increases; giant cell tumours may also arise. Revise bone tumours.

Treatment. Not everyone needs it. Bisphosphonates are first line; calcitonin is second line with an analgesic effect; denosumab has been used off-label in bisphosphonate intolerance; NSAIDs or paracetamol for pain; surgery for fractures, neural compression or sarcoma. Treatment is advised for bone deformities, weight-bearing bone or skull involvement, rapid progression and diffuse pain.

In primary hyperparathyroidism (PHPT), excess PTH increases bone resorption, raises calcium absorption through enhanced renal production of 1,25-dihydroxyvitamin D and reduces renal phosphate reabsorption. A single adenoma causes 80% to 85% of cases, multigland disease 10% to 15%, and carcinoma under 1%. Modern screening means most patients now present with mild or asymptomatic hypercalcaemia, but in regions with limited screening, skeletal and renal complications (osteitis fibrosa cystica, nephrolithiasis) still occur.

• Subperiosteal bone resorption (generalised osteopenia): the classic skeletal change, with generalised osteopenia.
• Salt-and-pepper skull: trabecular resorption interspersed with normal and sclerotic bone, with loss of distinction between the inner and outer tables.
• Brown tumours (osteoclastomas): lytic lesions with osteoclast-like giant cells and haemosiderin; the lesion of osteitis fibrosa cystica.
• Cortical tunnelling and loss of the corticomedullary junction.
• Today: the commonest skeletal finding on imaging is osteopenia; DEXA of the lumbar spine, hip and distal one-third radius is advised.

Surgery (parathyroidectomy) is indicated in all symptomatic patients, including those with nephrolithiasis, nephrocalcinosis, fragility fractures or osteoporosis. Asymptomatic patients qualify if age is under 50, serum calcium is more than 1.0 mg/dL above normal, creatinine clearance or eGFR is below 60, or the BMD T-score is -2.5 or lower. Imaging is for pre-operative localisation only; biochemistry makes the diagnosis. After surgery, hungry bone syndrome causes profound hypocalcaemia with hypophosphataemia and raised ALP.

As kidney function declines, a complex disorder of bone, mineral metabolism and cardiovascular health called CKD-mineral bone disorder (CKD-MBD) develops. Falling calcium and rising phosphate drive secondary hyperparathyroidism, typically with hypocalcaemia, hyperphosphataemia, raised FGF-23, reduced 1,25-dihydroxyvitamin D and high PTH. The skeletal result is renal osteodystrophy.

Osteoporosis is low bone mineral density caused by altered bone microstructure, predisposing to low-impact fragility fractures. Risk factors include increasing age, low body weight, smoking, family history, white or Asian race, early menopause, low physical activity and a prior minor-trauma fracture after age 40. See also menopause and HRT and corticosteroids.

• Treat a patient with a T-score of -2.5 or lower, or with osteopenia (T-score -1 to -2.5) and a 3% or higher hip-fracture risk on risk assessment; a personal fragility fracture can be treated without further testing.
• Correct vitamin D deficiency first; intravenous bisphosphonates are used if oral bisphosphonates are not tolerated.
• Do not repeat DEXA in women with a normal baseline scan; follow-up scans rarely change treatment.

• Looser zones = osteomalacia (pseudofractures), not Paget disease.
• Paget: ALP raised, calcium and phosphate normal. If calcium is high, think hyperparathyroidism.
• Cotton-wool skull = Paget; salt-and-pepper skull = hyperparathyroidism.
• Rugger jersey spine = renal osteodystrophy (secondary hyperparathyroidism).
• Brown tumour = osteitis fibrosa cystica from PTH excess, not a true neoplasm.
• Bisphosphonates are first line in Paget disease; treat only when symptomatic or at risk.
• Sudden pain or swelling in Paget = think osteosarcoma.
• Hypercalcaemia with suppressed PTH and a granulomatous history points to sarcoidosis, not bone disease.

Practise with NEET PG previous year questions and INI-CET previous year questions, and see the most repeated topics.