Postoperative zoledronic acid for osteoporosis in primary hyperparathyroidism: a randomized placebo-controlled study

Eur J Endocrinol. 2021 Aug 27;185(4):515-524. doi: 10.1530/EJE-21-0322.


Objective: In primary hyperparathyroidism (PHPT) with osteoporosis, bone mineral density (BMD) improves after parathyroidectomy. It is unclear whether combining surgery with postoperative bisphosphonate treatment can further improve bone health.

Design: This randomized, placebo-controlled study compared the effects of surgery alone and surgery combined with zoledronic acid on bone metabolism in PHPT with osteoporosis.

Methods: Fifty-six patients (f/m 47/9, mean age 68.4 years) with PHPT and osteoporosis were randomized 1-3 months after parathyroidectomy to receive a 2-year treatment of zoledronic acid or placebo. Dual-energy X-ray absorptiometry (DXA) and bone turnover markers (N-terminal propeptide of type 1 procollagen, C-terminal telopeptide of type 1 collagen, and alkaline phosphatase) were measured annually during the 2-year follow-up.

Results: Two years after parathyroidectomy, BMD was significantly higher in the zoledronic acid (ZOL) group compared with the placebo (PBO) group at the femoral neck (P = 0.045 for Z-score) and lumbar spine (P = 0.039 and 0.017 for T- and Z-scores, respectively). Bone turnover markers were significantly lower in the ZOL group (P < 0.001 for all markers). Of the 18 patients who had received bisphosphonates for >1 year before surgery, BMD improved significantly in the ZOL group both in the femoral neck and lumbar spine (n = 10; all P < 0.001-0.01), but in the PBO group, only in the lumbar spine (n = 8, P = 0.03), (P = 0.08-0.95 for between-group changes).

Conclusion: BMD increases after parathyroidectomy both with and without zoledronic acid but the increase is significantly higher with postoperative zoledronic acid.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Bone Density / drug effects
  • Bone Density Conservation Agents / administration & dosage
  • Combined Modality Therapy
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Finland
  • Humans
  • Hyperparathyroidism, Primary* / complications
  • Hyperparathyroidism, Primary* / drug therapy
  • Hyperparathyroidism, Primary* / surgery
  • Male
  • Middle Aged
  • Osteoporosis* / drug therapy
  • Osteoporosis* / etiology
  • Osteoporosis* / surgery
  • Parathyroidectomy
  • Postoperative Period
  • Treatment Outcome
  • Zoledronic Acid / administration & dosage*


  • Bone Density Conservation Agents
  • Zoledronic Acid