Endocrine Feedback Loop — Episode 52

“Osteopenia as a Surgical Indication in Primary Hyperparathyroidism”

Podcast Date: August 22, 2024
Host: Dr. Chase Hendrickson (Vanderbilt University)
Guests: Dr. Allison Myers (Albert Einstein College of Medicine) & Dr. Natalie Cusano (Lenox Hill Hospital, Zucker School of Medicine at Hofstra)
Journal Article Discussed: Frey, S., & Girard, M., "Parathyroidectomy improves bone density in women with primary hyperparathyroidism and preoperative osteopenia" — JCEM, June 2024

Episode Overview

This episode explores the benefits of parathyroid surgery (parathyroidectomy) in women with primary hyperparathyroidism (PHPT) who have osteopenia, analyzing a recent prospective cohort study from France. The panel discusses the clinical implications of expanding surgical candidacy beyond patients with overt osteoporosis to those with “just” osteopenia, the nuances of current guideline recommendations, and future research directions.

Key Discussion Points & Insights

1. Clinical Context of Primary Hyperparathyroidism (PHPT)

• Prevalence & Presentation
  • 80% of PHPT patients are asymptomatic at diagnosis, often found incidentally via lab findings. (02:37)
  • Classical symptomatic presentation ("bones, stones, groans, and moans") is now rare due to routine serum calcium measurements. (03:29)
• Changing Definitions
  • The emergence of “normocalcemic PHPT”—elevated PTH with normal calcium. (02:37, 03:29)
• Complications
  • Kidney stones and bone loss (osteopenia/osteoporosis) remain key concerns; fractures can occur even in “asymptomatic” cases, justifying routine screening. (03:29–04:34)

2. Guidelines on Surgery in Osteopenia vs. Osteoporosis

• Current Recommendations
  • Surgery is recommended for PHPT with osteoporosis, but not routinely for osteopenia, lacking decisive fracture risk data for the latter group.
  • Recent guideline updates suggest patients with a significant decline in bone density while being monitored—regardless of reaching the osteoporosis threshold—should be considered for surgery. (05:26)
• Cost-Effectiveness & Age
  • Evidence supports surgery for patients under 50; there’s debate and ongoing research regarding older patients. (05:26)
• Panel Consensus
  • “Guidelines are complicated…but the majority of patients with PHPT are postmenopausal women with a generally high prevalence of osteopenia. Changing guidelines would have a significant impact.” — Dr. Cusano (06:41)

3. Study Design & Methods

• Type: Prospective cohort of women with PHPT undergoing parathyroidectomy. (07:54)
• Population: 177 women (exclusions: males, incomplete data, non-primary hyperparathyroidism, etc.), mean age 62. (18:27)
• Definitions: Osteopenia/osteoporosis assessed by DXA T scores (not all postmenopausal—discussion around appropriateness of T vs. Z scores). (10:56)
• Procedures: Two experienced surgeons; surgical indications based on French (and similar US) guidelines. (11:18)
• Bone Density Measurements: Preoperative and one year post-op DXA; use of least significant change (LSC) threshold. (13:11)
  • “Clinically, I do measure bone density one year after a successful parathyroid surgery and start pharmacologic osteoporosis therapy at that time, if the bone density remains low.” — Dr. Cusano (13:00)
• Statistical Comments: Multiple confounders were listed but not statistically adjusted; spot urine calcium was used with imputation for 24-hour values. (16:05–17:35)

4. Results

• Population Stats (18:27)
  • Final analysis: 177 women
  • 20% normal BMD, rest split between osteopenia & osteoporosis.
  • Osteoporosis group was older and had more fractures; osteopenia group had higher BMI and fat %, more postmenopausal women.
• Perioperative and Biochemical Outcomes
  • Significant reduction in serum and urine calcium, and PTH after surgery; increase in phosphorus. (22:32)
  • High surgical “cure” rates based on biochemical normalization.
• Bone Mineral Density (BMD) Change
  • BMD improved at all skeletal sites post-op, most at lumbar spine, followed by hip, then forearm.
  • No statistically significant difference in absolute BMD improvement between osteoporosis and osteopenia cohorts.
    • In the osteopenia group, 86.8% had significant BMD gains at ≥1 site, especially those with higher preoperative bone turnover markers (P1NP, CTX).

  “Those with a BMD gain had a higher preoperative level of their bone turnover markers…” — Dr. Myers (23:52)

• Confounders Not Accounted For
  • Factors like race/ethnicity, lifestyle (smoking, activity), steroid use, and hormone replacement therapy missing or unaccounted. (18:27, 21:44)

5. Discussion and Clinical Implications

• Prevalence Comparison
  • High frequency of osteopenia and osteoporosis in the French cohort tracks with US data, though inclusion criteria and demographic diversity may differ. (25:59)
• Site Specificity of BMD Improvement
  • Trabecular bone (lumbar spine) sees more improvement than cortical bone (forearm), as cortical bone has a lower turnover rate and responds less to metabolic shifts.
    • “Trabecular bone…improves much more than cortical bone, which is the outer shell of bone…in the majority of studies in the literature, there have been significant improvements in bone density at the lumbar spine, less so at the hip, and little to any improvement at that distal one third radius.” — Dr. Cusano (27:17)
• Role of Bone Turnover Markers
  • High preoperative CTX or P1NP levels may predict who benefits most from surgery—plausible but not ready for guidelines due to assay variability and lack of standardized thresholds.
    • “It’s really hard to delineate a cutoff for bone turnover markers when surgery might be indicated…they’re not standardized.” — Dr. Cusano (29:55)

6. Limitations & Need for Further Study

• No Control Group
  • The absence of a medically managed (non-surgical) comparison group was a major limitation, complicating the ability to attribute gains solely to surgery. (30:48)
• Statistical Issues
  • No adjustment for baseline group differences (age, BMI, menopause, etc.)
• DXA Variability & Data Gaps
  • Not all scans done on site; missing data on certain measurements (e.g., the wrist), hormone replacement therapy, and other possible confounders.
• Generalizability Issues
  • Lack of demographic diversity; findings may not extend to more heterogeneous populations.
• Quality of Microarchitecture Assessment
  • DXA tells only part of the story; bone “quality” may not be reflected in BMD alone.

7. Should Guidelines or Practice Change?

• Current Take
  • The study adds important data showing that osteopenic women post-parathyroidectomy can experience robust BMD gains—comparable to those with osteoporosis.
• Guideline Impact
  • Not sufficient to prompt immediate change due to lack of fracture data, limitations noted, and absence of control arm.
• Practical Approach
  • The panel suggests continuing to individualize discussions about surgery, especially for osteopenic patients experiencing bone loss. Many patients still resist surgery despite its effectiveness and safety.
• Future Directions
  • Large, population-based, randomized studies are needed—especially with fracture endpoints and more population diversity.

“I do always speak about surgery [to osteopenic PHPT patients with declining BMD]...This leads to the literature that we can see significant improvements in bone density...I don’t think it quite changes any minds in terms of the guidelines as of yet.” — Dr. Cusano (35:27)

Notable Quotes & Memorable Moments

• Guideline Implications:

  “Given that the majority of patients with primary hyperparathyroidism are postmenopausal women with a generally high prevalence of osteopenia, changing the guidelines would have a significant impact on the number of parathyroid surgeries performed.” (06:34 — Dr. Cusano)

• Bone Response To Surgery:

  “Trabecular bone…improves much more than cortical bone…so, the lumbar spine is primarily trabecular bone...In the majority of studies…significant improvements [occur] at the lumbar spine, less so at the hip, and little to any improvement at that distal one third radius.” (27:17 — Dr. Cusano)

• Predicting Surgical Benefit:

  “It’s really hard to delineate a cutoff for bone turnover markers…they’re not standardized across all labs." (29:55 — Dr. Cusano)

• Practical Concerns:

  “Even though it’s a relatively straightforward surgery...a lot of patients don’t want to undergo surgery...there’s a lot in the literature that is reassuring if patients are not undergoing surgery.” (35:27 — Dr. Cusano)

• Study Strengths and Weaknesses:

  “My impression is that they embarked on something that we don’t know much about. So I think it’s a good start. Obviously, it doesn’t have the most robust sample size...but again, this is a starting point.” (32:38 — Dr. Myers)

Key Timestamps

• [02:37-03:29] Presentation and evolution of PHPT
• [05:26-07:15] Current guideline recommendations, gaps about osteopenia
• [07:54-13:11] Study design and methods dissection
• [18:27-24:22] Key findings, group comparisons, BMD results
• [27:17] Differences in bone response at different skeletal sites
• [29:55-30:48] Predictive value and limitations of bone turnover markers
• [32:38-34:14] Panel’s appraisal of study quality and its clinical value
• [35:27] Practical application and likelihood of changing practice/guidelines

Takeaways for Clinical Practice

• Women with osteopenia from PHPT may experience significant improvements in bone density after parathyroidectomy, similar to patients with osteoporosis.
• Current guidelines do not yet support routine surgery for osteopenic PHPT unless there’s documented BMD decline, but individualized discussion is warranted for surgery consideration.
• Improvements are most robust at trabecular-rich sites, especially the lumbar spine.
• Predicting responders based on bone turnover markers holds potential, but standardization is lacking.
• Larger, multi-ethnic, sufficiently powered studies with fracture and quality of life outcomes are needed before broadening surgical indications.

This detailed summary provides a comprehensive account of key topics, arguments, data, and expert perspectives from episode 52 of the Endocrine Feedback Loop podcast. It is intended as an in-depth substitute for listeners or clinicians who may not have time to hear the original episode.