Osteoporosis: Lest We Forget Secondary Causes Learning Objectives 1. Review screening recommendations 2. Know diagnostic criteria 3. Differentiate between various levels of workup 4. Apply knowledge to 3 case studies 5. Describe appropriate treatment regimens Paul Dassow, MD, MSPH Associate Professor Department of Family Medicine June 15, 2018 Screening (DEXA) Question 1: (USPSTF) USPSTF 1. All women at age 65 2. Women less than 65 who have the same fracture risk as a 65 yr old without additional risk factors 3. Data insufficient to recommend screening for men NOF 1. All women at age 65 2. All men at age 70 3. Women and men 50 and over with increased risk factors 4. All women and men 50 and over who experience a fracture Q: What does it mean to have the same risk of osteoporosis as a 65 year old? A: The risk of any osteoporotic fracture in the next 10 years for women who are 65, without additional risk factors, is 9.3%. Using a FRAX calculator, this risk can be calculated for any postmenopausal woman. Examples of risk equivalency in women 1. A 50 yo current smoker with BMI < 21, daily etoh use, parental fx hx 2. A 55 yo with parental fx hx 3. A 60 yo with daily etoh use and BMI < 21 4. A 60 yo current smoker with daily etoh use Question 2: (NOF) Q: What does with increased risk factors mean? A: It means realizing there is a long list of conditions and diseases that decrease bone density. (See chart) A few words about DEXA scans 1. Fracture risk increases exponentially with decreasing BMD 2. Diagnostic categories for men and women 50 and older 1. Osteopenia: T scores between -1 to -2.5 2. Osteoporosis: T scores <= -2.5 3. These criteria should not be used for those < 50 4. For those less than 50, Z scores of < -2 indicate low bone density for age. 1
T s and Z s Q: Is there a role for x-ray in the diagnosis of osteoporosis? A: The NOF recommends vertebral x-ray in the following clinical circumstances: 1. Women >=70 or men >=80 who have a T-score of < -1 at any site 2. Women 65-70 and men 70-80 who have a T- score of < -1.5 at any site 3. PM women and men >=50 with historical height loss > 1.5 (4cm) or prospective loss > 0.8 (2cm) 4. Current or ongoing glucocorticoid therapy Diagnosis of Osteoporosis Work Up For those 50 and older, a hip OR lumbar T score of <= -2.5 OR A fragility fracture at any site, at any age (A radius BMD can be used if hip or lumbar site is uninterpretable) UpToDate For all: CMP, CBC, Vit D and phosphorus For those with Z score less that -2 or other historical concerns, consider: TSH, PTH, 24 urine Ca, SPEP, Celiac Panel NOF Lab testing is indicated to exclude secondary causes of osteoporosis Consider: All labs to the left, plus BTM s, testosterone (men), iron, prolactin, tryptase, homocysteine, urinary free cortisol Bone Turnover Markers (BTM s) Indicate at what rate bone turnover is occurring Resorption: C and N telopeptides (NTX, CTX) Formation: procollagen propeptides (PICP, PINP) and Osteocalcin (OC) BTM s typically fall rapidly with therapy. Higher levels correlate with higher bone turnover. Higher bone turnover in those > 50 correlates with lower BMD. No current consensus re: their use in Dx or treatment. Can be used to assess compliance and absorption (baseline and 6 months) Can be used to assess need to restart therapy after holiday Clinical Cases All cases represent real patients who receive care in our clinic 2
Case 1 Case 1 - NR NR is a 37 yo female who presented to clinic with a c/o back pain for 1 day. She works as a bus driver and states that as she helped lift a disabled man (~170 lbs) off her bus, she felt a pop in her mid back. She denies any bladder or bowel changes, but does c/o radiation down her L leg. NR has a h/o GERD, Grave s Dz, depression, 16 py tob use, and asthma. Pt had a TAH/BSO at age 27 for fibroids, and complete thyroidectomy at age 35 She reports taking estrogen for about a year after her hyst and then stopped due to concerns about breast cancer. Her Family Doc agreed. Meds: levothyroxine 175mcg, sertraline 50mg, omeprazole 20, albuterol MDI prn Pt s physical exam was unremarkable except for her obesity (243lbs, BMI 43), mod tenderness at the T11-L1 area and severe limitation of flex/exten of the spine Questions 1. Does this history warrant an order for a DEXA scan? Yes If so, why? No 2. Assuming this fracture is related to low bone density, what do you think may be its cause? a) Estrogen deficiency b) Hyperthyroidism c) Kidney disease d) Vitamin D def e) Chronic PPI use Case 2 Case 2 - TR TR is a 43 yo male of Native American descent who come to you with concerns about his bone density. He paid for one of those full body scans and says that they told him his bones looked weak. He asks you about getting a DEXA scan. TR does not smoke nor use alcohol. He does not take any medications. He says he tries to eat healthy he does eat some meat. He takes a multivitamin daily. TR has a h/o OCD sxs but currently treats this with meditation. He has had 2 kidney stones, at age 33 and 38. He tries to hydrate well with water. You read the papers he brings you and note that a heel ultrasound was done which gave a T score of -2.8 Do you order the DEXA scan? Yes No 3
Case 2 - TR DEXA results: T score at hip -2.3 T score at spine -2.8 Z score at hip -3.2 Z score at spine -3.7 Initial lab results: CBC normal Glu 98 Na 133 Cl 111 K 3.2 CO 13 Ca 8.9 Cr 0.9 LFT s wnl Vit D 56 Question At this point, you suspect what underlying cause for his osteoporosis? a) Renal Tubular Acidosis b) Chronic Alcoholism c) Vitamin D overuse d) Undiagnosed diabetes e) Compulsive use of apple cider vinegar BA is a 58 yo woman who presents after a falling and breaking her wrist. She states she missed her last step out her back door and fell backwards on the concrete. She went to the ER last night and was placed in a splint and told to f/u with her PCP. She went through natural menopause at 51 and chose not to treat her hot flushes with hormones Case 3 Case 3 - BA Case 3 - BA BA has no h/o smoking. She drinks etoh rarely. She has a diagnosis of HTN (on lisinopril 20) and obesity (BMI 34). She works as a research assistant at the local college and states she generally feels in good health. Should this be considered a fragility fracture? Yes NO Initial lab eval: CBC wnl CMP wnl except for a Ca of 11.8 Vit D 24 DEXA scan: Spine T-score -1.6 Hip T-score -2.5 At this point, you suspect an underlying cause of: a) Vitamin D def b) Age related osteoporosis c) Multiple Myeloma d) Familial hypocalciuric hypercalcemia e) Primary hyperparathyroidism 4
Pause for Questions Case 1 revisited (Our 37 yo with a T12 compression fracture) The official definition of a fragility fracture is one that is sustained during a low trauma event. This includes falls from standing. Helping to move a 170 lb person is a judgement call a scan was not originally ordered. NR s DEXA results Additional labs Estrogen 18 (100-300) PTH 45 (20-70) Vitamin D 14.6 (30-100) TSH <0.02 (0.34-5.6) 24 hr urine Ca 143 mg (100 300) Phosphorus wnl So what was the cause of NR s osteoporosis? Likely a perfect multifactorial storm: Low estrogen for 10 yrs. Estrogen known to influence trabecular bone > cortical bone Low Vitamin D. Unknown duration. Iatrogenic hyperthyroidism. Record review noted TSH of 0.024 and T4 of 1.44 (0.5-1.24) in June of 2016. This was recorded 3 months after an increase in her supplement due to elevated TSH. Repeat T4 was 1.64. Tobacco use Treatment for Case 1 Discussion of 1. Supplementing estrogen would include tob cessation, WHI data on estrogen only risk and breast Ca, clotting risk. Estrogen FDA indicated for prevention and not treatment. 2. Vitamin D supplementation 3. Lowering levothyroxine dose 4. Starting Bisphosphonate 5
Revisiting Case 2 (Our 43 yo male with asymptomatic low BMD) DEXA results: T score at hip -2.3 T score at spine -2.8 Z score at hip -3.2 Z score at spine -3.7 Does TR have osteoporosis? What is the cause of TR s Low BMD? Initial lab results: CBC normal Glu 98 Na 133 Cl 111 K 3.2 CO 13 Ca 8.9 Cr 0.9 LFT s wnl Vit D 56 At this point, you suspect what underlying cause for his osteoporosis? a) Renal Tubular Acidosis b) Chronic Alcoholism c) Vitamin D overuse d) Undiagnosed diabetes e) Compulsive use of apple cider vinegar Renal Tubular Acidosis Chronic non anion-gap acidosis Comes in 3 varieties: 1. Type 1 inability to acidify urine. Associated with autoimmune dz. Associated with renal calcification and renal stones. 2. Type 2 inability to reabsorb filtered bicarb. Associated with damage to proximal tubule, usually light chain dz or chemo agents. Mild acidemia. 3. Type 4 hypoaldosteronism. Due to either lack of production or resistance. Associated with high K, mild acidemia, and Case 2 After further evaluation, TR was diagnosed with idiopathic type 1 RTA Serum ph 7.28 Urine ph 6.4 (inappropriately alkaline) No alkalization of urine with bicarb infusion High calcium on 24 hour urine Negative tests for autoimmune disorders (Sjogrens, RA, lupus) Treatment for Case 2 Daily potassium citrate supplementation to a bicarb level of 22-24 Renal US (at diagnosis and periodically thereafter) Repeat DEXA in 2 years Ca/Vit D supplement (1000/800) daily FRAX scores did not meet criteria for bisphosphonate therapy (MORES) Revisiting Case 3 (Our 58 yo who broke her wrist) Initial lab eval: CBC wnl CMP wnl except for a Ca of 11.8 Vit D 24 DEXA scan: Spine T-score -1.6 Hip T-score -2.5 6
Case 3 Additional lab eval At this point, you suspect an underlying cause of: a) Vitamin D def b) Age related osteoporosis c) Multiple Myeloma d) Familial hypocalciuric hypercalcemia e) Primary hyperparathyroidism What tests would you order to help with this diagnosis? SPEP normal 24 hour urine calcium 442 (100-300) PTH 140 (20 70) Phosphorus normal Lumbar spine film Evidence of old compression fractures at L1 and L2 Primary Hyperparathyroidism (PHPT) PHPT is most often clinically silent Diagnosed typically by an incidental elevated calcium level, or less commonly low BMD Clinical sxs if calcium levels rise above 12: Anorexia, nausea, kidney stones, depression, fatigue stones, bones, abdominal groans, psychic moans Parathyroid crisis Typically calcium levels above 15 CNS depression, from somnolence to coma Treatment for Case 3 Surgical removal of parathyroid gland This can now be done in a minimally invasive fashion Close monitoring of serum calcium levels Renal Ultrasound Vitamin D supplementation Repeat Dexa in 2 years Consider Bisphosphonate correction of HPT should lead to increases in BMD Further treatment related considerations 7
Bisphosphonates Bisphosphonates Still first line therapy for most people with diagnosed osteoporosis (after secondary causes treated) Contraindications egfr < 35 Cannot sit upright for 30 min (oral) Esophageal dysfunction (oral) GI anastomoses (oral) Poorly absorbed orally, < 1%. Should be taken on an empty stomach, not at the same time as Ca/Vit D alendronate (Fosamax) 10 qd, 70 qwk, available in an oral solution (75ml) $108 risedronate (Actonel) 5 qd, 35 qwk, 150 qm $800 ibandronate (boniva) 150 qm, 3mg q3m (IV) $280 zoledronic acid (Reclast) 5 qyr (IV) $1100 Other 1 RCT showed Fosamax inc BMD at 1 yr more than Actonel 1 cohort study showed Actonel had better fx reduction than Fosamax at 1 yr Boniva not shown to decrease hip fx risk. Not recommended as initial bisphosphonate Parathyroid hormone analogs RANKL Inhibitors teriparatide (Forteo) 20 mcg SC qd Safety and efficacy greater than 2 yrs not established $3000 per month Black box warning for osteosarcoma noted in rat studies. No renal dosing abaloperatide (Tymlos) 80 mcg SC qd Safety and efficacy greater than 2 yrs not established 1800 per month Black box warning for osteosarcoma noted in rat studies. No renal dosing denosumab (Prolia) 60mg SC q6mo $2400 per year No renal dosing No black box warnings For those with multiple fracture risk factors or who have failed other osteoporosis tx Medication Holidays Questions? Current consensus for bisphosphonates supports: For low risk women (no fx, BMD > -3.5) Stopping oral tx after 5yrs, IV treatment after 3 yrs For higher risk women Stopping oral tx after 10 yrs, IV treatment after 6 yrs As for restarting therapy No data to support one strategy over another Restart after 5 yrs Restart after 2 DEXA s show decrease BMD Restart after BTM s reach levels above normal premenopausal range 8