Idiopathic Osteoporosis

Idiopathic osteoporosis is osteoporosis with fragility fractures in children or in adults before the age of 50 years (premenopausal women and men) in whom no secondary cause is found after thorough investigation. It is a diagnosis of exclusion.

Idiopathic juvenile osteoporosis presents in prepubertal children (usually 8 to 14 years) with back pain, vertebral compression fractures and metaphyseal fractures. It is rare and often remits spontaneously around or after puberty. Idiopathic osteoporosis in young adults is also rare and may be heritable.

Some patients have variants in genes that cause skeletal fragility (LRP5, WNT1, COL1A1, COL1A2, PLS3).

Pathophysiology.

Bone histomorphometry shows low bone turnover and reduced formation in many (osteoblast dysfunction) and high turnover with hypercalciuria in a few. Genetic causes are found in a minority.

Remission after puberty in children suggests dependence on pubertal bone accrual.

• Back pain, vertebral compression fractures, and long bone fractures after low trauma, with gait disturbance and kyphosis in children.
• Height loss and low bone mass on imaging. No signs of secondary causes.

Red flags.

• Multiple fractures with deformity.
• Pain with bone lesions, weight loss, anaemia or raised calcium.

• Exclude secondary and heritable causes: calcium, phosphate, parathyroid hormone, 25-hydroxyvitamin D, alkaline phosphatase, thyroid function, full blood count, ESR, protein electrophoresis, coeliac serology, kidney and liver function, cortisol tests, sex steroids, prolactin and 24-hour urinary calcium.
• DXA with Z-scores (age matched), spine radiographs for vertebral fractures.
• Genetic testing for osteogenesis imperfecta and other osteoporosis genes (COL1A1, COL1A2, LRP5, WNT1, PLS3). Bone biopsy with histomorphometry in selected cases.
• Family history and examination for blue sclerae, hypermobility and dentinogenesis imperfecta.

Differential diagnosis.

• Osteogenesis imperfecta, Ehlers-Danlos and Marfan syndromes.
• Leukaemia, other malignancy and chronic inflammatory disease in children.
• Glucocorticoid exposure, coeliac disease, hypogonadism and hyperparathyroidism.

• Calcium and vitamin D (vitamin D 800 to 2000 units daily to keep 25-hydroxyvitamin D over 50 nmol/L, 20 ng/mL), weight bearing activity and physiotherapy.
• Children: observe if fractures are few and symptoms mild, since remission is common. Severe or progressive disease: intravenous bisphosphonate (pamidronate or zoledronic acid) in a paediatric bone service, with analgesia and spinal care.
• Adults: bisphosphonate (alendronate 70 mg weekly) for recurrent fractures, with caution in women who may become pregnant. Teriparatide 20 micrograms subcutaneously daily for up to 24 months for severe disease.
• Evidence for treatment is limited to observational studies.
• Genetic counselling when a variant is found. Address pain, mobility and psychosocial needs.

Special groups. Pregnancy: plan with bone and obstetric teams, since fractures can occur in late pregnancy.

Monitoring. Children: growth, pain and spine imaging every 6 to 12 months. Adults: DXA every 1 to 2 years and fracture review.

Referral and escalation. Paediatric bone service for children; endocrinology or metabolic bone service for adults; clinical genetics.