Is the presence of strontium in urine concerning, and what evaluation or management is needed, especially if the patient is taking strontium ranelate or has renal impairment?

Strontium in Urine: Clinical Significance and Management

Is Urinary Strontium Concerning?

The presence of strontium in urine is generally not concerning in healthy individuals, as strontium is a naturally occurring trace element with normal urinary excretion; however, elevated levels warrant evaluation in patients taking strontium ranelate or those with renal impairment due to risk of bone toxicity. 1, 2

Normal Reference Values

• Urinary strontium follows a log-normal distribution with a geometric mean of 143.9 μg/L (95% confidence interval: 40.9-505.8 μg/L) in healthy Japanese adults. 2
• Similar reference values have been confirmed across populations, with geometric mean of 143.9 μg/L and range of 40.9-505.8 μg/L serving as guidelines for health screening. 1
• Urine is the preferred monitoring matrix given strontium's short biological half-life and primary renal excretion route. 1

High-Risk Populations Requiring Evaluation

Patients Taking Strontium Ranelate

Strontium ranelate therapy poses significant risks that necessitate careful monitoring, particularly in patients with any degree of renal impairment. 3, 4, 5

• Strontium ranelate is used for osteoporosis treatment but was historically abandoned in the 1950s due to bone mineralization disorders at high doses. 5
• The British Society of Gastroenterology guidelines list strontium ranelate as a treatment option for osteoporosis in primary biliary cholangitis, but only after first-line bisphosphonates. 3
• Strontium ranelate increases venous thromboembolism risk by 50%, including pulmonary embolism. 5
• Elevated serum creatine kinase occurs in 30% of patients on strontium ranelate. 5

Patients with Renal Impairment

Renal impairment dramatically increases the risk of strontium accumulation and subsequent bone toxicity, making urinary strontium monitoring critical in this population. 4, 6

• Patients with chronic renal failure accumulate strontium in bone, which causes osteomalacia—a mineralization defect characterized by increased osteoid thickness, reduced mineralization rate, and pathological fractures. 4
• In experimental chronic renal failure rats, strontium-induced osteomalacia developed within 2 weeks of exposure, with significantly increased osteoid perimeter, area, and thickness. 4
• After 12 weeks of strontium exposure in renal failure, mineralization was severely affected with lower double-labeled surface, reduced mineral apposition rate, decreased bone formation rate, increased osteoid maturation time, and prolonged mineralization lag time. 4
• Strontium accumulation in renal failure also reduces osteoblast number and suppresses parathyroid hormone synthesis or secretion. 4
• Serum alkaline phosphatase rises significantly in strontium-loaded patients with renal impairment, reflecting bone, liver, and intestinal isoenzyme elevation. 4

When to Measure Urinary Strontium

Measure urinary strontium in the following clinical scenarios:

• Any patient taking strontium ranelate, especially if they have reduced glomerular filtration rate. 4, 5
• Patients with chronic kidney disease who develop unexplained bone pain, fractures, or elevated alkaline phosphatase. 4, 6
• Patients on long-term dialysis with bone disease, as strontium accumulates in end-stage renal disease. 3, 6
• Occupational or environmental exposure concerns requiring biological monitoring. 1, 2

Management Algorithm

If Urinary Strontium is Elevated in a Patient Taking Strontium Ranelate:

1. Immediately discontinue strontium ranelate if the patient has any degree of renal impairment (eGFR <60 mL/min/1.73m²). 4, 5
2. Assess renal function with serum creatinine and calculate eGFR using KDIGO criteria. 3
3. Check serum alkaline phosphatase, creatine kinase, and parathyroid hormone levels. 4
4. Obtain bone mineral density and consider bone biopsy if osteomalacia is suspected clinically. 4
5. After strontium withdrawal, bone lesions reverse within 2-8 weeks as bone strontium content decreases by approximately 18%, with normalization of serum alkaline phosphatase and PTH. 4

If Urinary Strontium is Elevated in a Patient with Renal Impairment (Not on Strontium Ranelate):

1. Investigate environmental or occupational sources of strontium exposure. 1
2. Review all medications and supplements for strontium content. 5
3. Monitor bone health with alkaline phosphatase, PTH, and bone mineral density. 4
4. Consider switching osteoporosis therapy to bisphosphonates if strontium ranelate was recently used. 3

Critical Pitfalls to Avoid

• Do not continue strontium ranelate in patients with reduced renal function, as the risk of osteomalacia far outweighs potential benefits. 4, 5
• Do not assume elevated alkaline phosphatase in a patient on strontium ranelate is solely from bone; check liver and intestinal isoenzymes. 4
• Do not use strontium ranelate as first-line osteoporosis therapy when bisphosphonates are available and appropriate. 3
• Long-term adverse effects of strontium on bone (osteomalacia, pathological fractures) remain inadequately documented in humans, warranting extreme caution. 5
• Neurological and muscular adverse effects of strontium are inadequately documented despite animal data showing these effects. 5

Monitoring During Strontium Ranelate Therapy (If Continued)

• Measure serum creatinine and calculate eGFR every 3 months. 3
• Check serum creatine kinase, alkaline phosphatase, and PTH every 6 months. 4
• Monitor for venous thromboembolism symptoms (leg swelling, chest pain, dyspnea). 5
• Assess bone mineral density annually. 3
• Discontinue immediately if eGFR declines below 60 mL/min/1.73m² or if serum creatinine increases by ≥0.3 mg/dL within 48 hours (KDIGO AKI Stage 1 criteria). 3