Muscle Aches: A ray of Muscle Aches: A ray of hopehope

Mary ThomasonMary Thomason

Feb. 25, 2004Feb. 25, 2004

Case PresentationCase PresentationHPI: 43 yo female with generalized muscle HPI: 43 yo female with generalized muscle

aches. Notes significant pain throughout aches. Notes significant pain throughout body the day after exercising. Also notes body the day after exercising. Also notes fatigue, greatest upon first awakening. fatigue, greatest upon first awakening.

PMH:PMH: FibromyalgiaFibromyalgiaIrritable bowel syndromeIrritable bowel syndromeHypothyroidHypothyroidDepression/AnxietyDepression/AnxietyAsthmaAsthmaSleep apnea on CPAPSleep apnea on CPAPMigraine HAMigraine HAGERDGERD

Case PresentationCase Presentation ROS: Describes herself as sensitive to sun. ROS: Describes herself as sensitive to sun.

Diary products cause diarrhea.Diary products cause diarrhea. Social Hx: No Tob or ETOH. Works in Social Hx: No Tob or ETOH. Works in

Home Health.Home Health. Family Hx: Father, early CAD. Mother, Family Hx: Father, early CAD. Mother,

premenopausal breast CA, hypothyroid, premenopausal breast CA, hypothyroid, hyperparathyroid. hyperparathyroid.

Medications: Ca with vit D 500/200mg PO Medications: Ca with vit D 500/200mg PO QD, Multivitamin QD, Synthroid 200mcg QD, Multivitamin QD, Synthroid 200mcg QD, Prilosec 20mg BID, Zoloft 150mg QD.QD, Prilosec 20mg BID, Zoloft 150mg QD.Clonazepam prn, Levsin prn, Ibuprofen Clonazepam prn, Levsin prn, Ibuprofen prn, Midrin prn, Albuterol prnprn, Midrin prn, Albuterol prn

Case PresentationCase Presentation PEPE Vitals: BP 126/80, P 80Vitals: BP 126/80, P 80

Musculoskeletal: Very few tender Musculoskeletal: Very few tender points, full range of motion of all points, full range of motion of all

joints joints without swelling or without swelling or erythema, muscle erythema, muscle strength is 5/5 strength is 5/5 throughout.throughout.

Lab results: TSH 3.22, Ca 9.0 (8.5-Lab results: TSH 3.22, Ca 9.0 (8.5-10.2), phos 2.5 (2.5-3.7), PTH 75 (15-10.2), phos 2.5 (2.5-3.7), PTH 75 (15-65), 25-vitamin D 11 (20-57).65), 25-vitamin D 11 (20-57).

BMD: Lumbar T +1.7, Femur T+2.0BMD: Lumbar T +1.7, Femur T+2.0

ObjectivesObjectives Vitamin D MetabolismVitamin D Metabolism Actions of Vitamin DActions of Vitamin D Causes of Vitamin D deficiencyCauses of Vitamin D deficiency Prevalence of Vitamin D deficiencyPrevalence of Vitamin D deficiency Presentation of Vitamin D deficiencyPresentation of Vitamin D deficiency Diagnosis of Vitamin D deficiencyDiagnosis of Vitamin D deficiency Treatment of Vitamin D deficiencyTreatment of Vitamin D deficiency

This talk has not been sponsored by any This talk has not been sponsored by any organizations.organizations.

ObjectivesObjectives Vitamin D MetabolismVitamin D Metabolism Actions of Vitamin DActions of Vitamin D Causes of Vitamin D deficiencyCauses of Vitamin D deficiency Prevalence of Vitamin D deficiencyPrevalence of Vitamin D deficiency Presentation of Vitamin D deficiencyPresentation of Vitamin D deficiency Diagnosis of Vitamin D deficiencyDiagnosis of Vitamin D deficiency Treatment of Vitamin D deficiencyTreatment of Vitamin D deficiency

ObjectivesObjectives

Vitamin D MetabolismVitamin D Metabolism Actions of Vitamin DActions of Vitamin D Causes of Vitamin D deficiencyCauses of Vitamin D deficiency Prevalence of Vitamin D deficiencyPrevalence of Vitamin D deficiency Presentation of Vitamin D deficiencyPresentation of Vitamin D deficiency Diagnosis of Vitamin D deficiencyDiagnosis of Vitamin D deficiency Treatment of Vitamin D deficiencyTreatment of Vitamin D deficiency

ObjectivesObjectives

Vitamin D MetabolismVitamin D Metabolism Actions of Vitamin DActions of Vitamin D Causes of Vitamin D deficiencyCauses of Vitamin D deficiency Prevalence of Vitamin D deficiencyPrevalence of Vitamin D deficiency Presentation of Vitamin D deficiencyPresentation of Vitamin D deficiency Diagnosis of Vitamin D deficiencyDiagnosis of Vitamin D deficiency Treatment of Vitamin D deficiencyTreatment of Vitamin D deficiency

Causes of Vitamin D Causes of Vitamin D DeficiencyDeficiency

Reduced Vitamin D intakeReduced Vitamin D intake Recommended Vitamin D intakeRecommended Vitamin D intake Historial InformationHistorial Information

Reduced Cutaneous Vitamin D Reduced Cutaneous Vitamin D productionproduction

Reduced Vitamin D absorptionReduced Vitamin D absorption Increased Hepatic catabolismIncreased Hepatic catabolism Decreased endogenous synthesisDecreased endogenous synthesis GeneticGenetic

Causes of Vitamin D Causes of Vitamin D DeficiencyDeficiency

Reduced Vitamin D intakeReduced Vitamin D intake Recommended Vitamin D intakeRecommended Vitamin D intake Historial InformationHistorial Information

Reduced Cutaneous Vitamin D Reduced Cutaneous Vitamin D productionproduction

Reduced Vitamin D absorptionReduced Vitamin D absorption Increased Hepatic catabolismIncreased Hepatic catabolism Decreased endogenous synthesisDecreased endogenous synthesis GeneticGenetic

Daily Vitamin D Recommended Daily Vitamin D Recommended IntakeIntake

1000 IU/day minimum requirement 1000 IU/day minimum requirement (some say 2000 IU/d to 5000 IU/d)(some say 2000 IU/d to 5000 IU/d)

Recommendations:Recommendations: 200 IU/d <50 yo200 IU/d <50 yo 400 IU/d 51-70 yo400 IU/d 51-70 yo 600 IU/d >70 yo600 IU/d >70 yo

Historical InformationHistorical Information 1717thth-19-19thth centuries Vitamin D centuries Vitamin D

deficiency was problematicdeficiency was problematic 1930-1950s food fortification initiated 1930-1950s food fortification initiated

(Milk, bread, hot dogs, soda, and (Milk, bread, hot dogs, soda, and beer)beer)

1950 outbreak of vitamin D 1950 outbreak of vitamin D intoxication in young children of Great intoxication in young children of Great Britain resulted in banning of Britain resulted in banning of fortification in many US foods and all fortification in many US foods and all most all of European foods.most all of European foods.

Reduced Vitamin D intakeReduced Vitamin D intake

Fatty Fishes (Salmon)/ Liver/ eggFatty Fishes (Salmon)/ Liver/ egg Foods Fortified with Vitamin D Foods Fortified with Vitamin D

Milk (select other dairy products)Milk (select other dairy products) CerealsCereals Orange Juice -newOrange Juice -new

Food IU %DV *

Cod Liver Oil, 1 Tbs. 1,360 IU 340

Salmon, 3.5 oz 360 IU 90

Mackerel, 3.5 oz 345 IU 90

Sardines, 3.5 oz 270 IU 70

Eel, 3.5 oz 200 IU 50

Milk/fortified OJ, 1 c 98 IU 25

Margarine, 1 Tbs. 60 IU 15

Cereal grain bars 50 IU 10

Pudding 50 IU 10

Dry cereal 40-50 IU 10

Liver, beef, 3.5 oz 30 IU 8

Egg (vitamin D in yolk) 25 IU 6

Causes of Vitamin D Causes of Vitamin D DeficiencyDeficiency

Reduced Vitamin D intakeReduced Vitamin D intake Recommended Vitamin D intakeRecommended Vitamin D intake Historial InformationHistorial Information

Reduced Cutaneous Vitamin D Reduced Cutaneous Vitamin D productionproduction

Reduced Vitamin D absorptionReduced Vitamin D absorption Increased Hepatic catabolismIncreased Hepatic catabolism Decreased endogenous synthesisDecreased endogenous synthesis GeneticGenetic

Reduced Cutaneous Vitamin D Reduced Cutaneous Vitamin D ProductionProduction

Reduced Cutaneous Vitamin D Reduced Cutaneous Vitamin D ProductionProduction

Increased melanin pigmentationIncreased melanin pigmentation Sunscreen use (SPF 8 and greater Sunscreen use (SPF 8 and greater

reduces vitamin D production by 95%) reduces vitamin D production by 95%) Winter months at higher latitudes Winter months at higher latitudes

(greater than 38 degrees few UVB (greater than 38 degrees few UVB photons penetrate the atmosphere)photons penetrate the atmosphere)

Poor production in elderly skin (fourfold Poor production in elderly skin (fourfold reduction in production >70 yo)reduction in production >70 yo)

Causes of Vitamin D Causes of Vitamin D DeficiencyDeficiency

Reduced Vitamin D intakeReduced Vitamin D intake Recommended Vitamin D intakeRecommended Vitamin D intake Historial InformationHistorial Information

Reduced Cutaneous Vitamin D Reduced Cutaneous Vitamin D productionproduction

Reduced Vitamin D absorptionReduced Vitamin D absorption Increased Hepatic catabolismIncreased Hepatic catabolism Decreased endogenous synthesisDecreased endogenous synthesis GeneticGenetic

Reduced Vitamin D Reduced Vitamin D AbsorptionAbsorption

Gastrectomy/ bowel surgery Gastrectomy/ bowel surgery (including surgery for morbid (including surgery for morbid obesity)obesity)

Celiac SprueCeliac Sprue Inflammatory Bowel DiseaseInflammatory Bowel Disease Advanced Cystic Fibrosis (due to fat Advanced Cystic Fibrosis (due to fat

malabsorption)malabsorption)

Causes of Vitamin D Causes of Vitamin D DeficiencyDeficiency

Reduced Vitamin D intakeReduced Vitamin D intake Recommended Vitamin D intakeRecommended Vitamin D intake Historial InformationHistorial Information

Reduced Cutaneous Vitamin D Reduced Cutaneous Vitamin D productionproduction

Reduced Vitamin D absorptionReduced Vitamin D absorption Increased Hepatic catabolismIncreased Hepatic catabolism Decreased endogenous synthesisDecreased endogenous synthesis GeneticGenetic

Increased Hepatic Increased Hepatic CatabolismCatabolism

Severe Liver diseaseSevere Liver disease Medications that increase P-450 Medications that increase P-450

enzymesenzymes Anticonvulsants (phenobarbital, Anticonvulsants (phenobarbital,

phenytoin, carbamazepine)phenytoin, carbamazepine) AlcoholAlcohol IsoniazidIsoniazid TheophyllineTheophylline RifampinRifampin

Causes of Vitamin D Causes of Vitamin D DeficiencyDeficiency

Reduced Vitamin D intakeReduced Vitamin D intake Recommended Vitamin D intakeRecommended Vitamin D intake Historial InformationHistorial Information

Reduced Cutaneous Vitamin D Reduced Cutaneous Vitamin D productionproduction

Reduced Vitamin D absorptionReduced Vitamin D absorption Increased Hepatic catabolismIncreased Hepatic catabolism Decreased endogenous synthesisDecreased endogenous synthesis GeneticGenetic

Decreased Endogenous Decreased Endogenous SynthesisSynthesis

Renal Failure (nephrotic syndrome & Renal Failure (nephrotic syndrome & dialysis)dialysis)

Causes of Vitamin D Causes of Vitamin D DeficiencyDeficiency

Reduced Vitamin D intakeReduced Vitamin D intake Recommended Vitamin D intakeRecommended Vitamin D intake Historial InformationHistorial Information

Reduced Cutaneous Vitamin D Reduced Cutaneous Vitamin D productionproduction

Reduced Vitamin D absorptionReduced Vitamin D absorption Increased Hepatic catabolismIncreased Hepatic catabolism Decreased endogenous synthesisDecreased endogenous synthesis GeneticGenetic

Genetic Genetic

Type 1 Vitamin D dependent RicketsType 1 Vitamin D dependent Rickets Type 2 Vitamin D dependent RicketsType 2 Vitamin D dependent Rickets

ObjectivesObjectives

Vitamin D MetabolismVitamin D Metabolism Actions of Vitamin DActions of Vitamin D Causes of Vitamin D deficiencyCauses of Vitamin D deficiency Prevalence of Vitamin D deficiencyPrevalence of Vitamin D deficiency Presentation of Vitamin D deficiencyPresentation of Vitamin D deficiency Diagnosis of Vitamin D deficiencyDiagnosis of Vitamin D deficiency Treatment of Vitamin D deficiencyTreatment of Vitamin D deficiency

Prevalence of Vitamin D Prevalence of Vitamin D deficiencydeficiency

JAMA, 1995, Vol. 274, No 21, pg 1683-6JAMA, 1995, Vol. 274, No 21, pg 1683-6 Baltimore, MDBaltimore, MD Age >65 yoAge >65 yo 224 patients: 116 confined indoors x 6 mon 224 patients: 116 confined indoors x 6 mon

(52 homebound, 64 NH), 128 ambulatory(52 homebound, 64 NH), 128 ambulatory 48% of sunlight deprived vit D <10ng/mL 48% of sunlight deprived vit D <10ng/mL

(38% of nursing home, 54% homebound)(38% of nursing home, 54% homebound) 83% of nursing home took RDA 83% of nursing home took RDA

recommended amount of vit D verses 36% recommended amount of vit D verses 36% of homebound (although no correlation of homebound (although no correlation between vit D intake and vit D status)between vit D intake and vit D status)

Prevalence of Vitamin D Prevalence of Vitamin D deficiencydeficiency

NEJM, 1998; vol 338, no 12, 777-783NEJM, 1998; vol 338, no 12, 777-783 Inpatient General Medicine Ward, MAInpatient General Medicine Ward, MA 290 Patients: 150 March, 140 Sept.290 Patients: 150 March, 140 Sept. Age 18 to 95 yoAge 18 to 95 yo 57% Vitamin D deficient (15 ng/mL), 57% Vitamin D deficient (15 ng/mL),

22% severely (<8ng/mL)22% severely (<8ng/mL) Of the group <65 yo without risk factors Of the group <65 yo without risk factors

42% were Vitamin D deficient42% were Vitamin D deficient 63% in March and 49% in Sept63% in March and 49% in Sept

Prevalence of Vitamin D Prevalence of Vitamin D DeficiencyDeficiency

Am. Journal of Medicine Am. Journal of Medicine 2002;122:659-622002;122:659-62 Boston, MA; young healthy adultsBoston, MA; young healthy adults 165 end of winter, 142 end of summer165 end of winter, 142 end of summer In all age groups, Vitamin D insufficiency In all age groups, Vitamin D insufficiency

(20ng/mL) more common at end of (20ng/mL) more common at end of winter 30% verses end of summer 11%winter 30% verses end of summer 11%

36% of young adults aged 18-29 had 36% of young adults aged 18-29 had vitamin D deficiency at the end of wintervitamin D deficiency at the end of winter

Prevalence of Vitamin D Prevalence of Vitamin D DeficiencyDeficiency

Mayo Clinic Proceedings, ‘03; 78:1463-70Mayo Clinic Proceedings, ‘03; 78:1463-70 University Outpatient Clinic Minneapolis, MNUniversity Outpatient Clinic Minneapolis, MN 150 patients: 83 immigrant, 67 150 patients: 83 immigrant, 67

nonimmigrantnonimmigrant Age 10-65 yearsAge 10-65 years 2 months of nonspecific persistent 2 months of nonspecific persistent

musculoskeletal painmusculoskeletal pain 93% of all patients lack Vitamin (<20 ng/mL)93% of all patients lack Vitamin (<20 ng/mL) 28% were severely deficient (<8 ng/mL)28% were severely deficient (<8 ng/mL)

ObjectivesObjectives

Vitamin D MetabolismVitamin D Metabolism Actions of Vitamin DActions of Vitamin D Causes of Vitamin D deficiencyCauses of Vitamin D deficiency Prevalence of Vitamin D deficiencyPrevalence of Vitamin D deficiency Presentation of Vitamin D deficiencyPresentation of Vitamin D deficiency Diagnosis of Vitamin D deficiencyDiagnosis of Vitamin D deficiency Treatment of Vitamin D deficiencyTreatment of Vitamin D deficiency

Presentation of Vitamin D Presentation of Vitamin D DeficiencyDeficiency

Chronic nonspecific musculoskeletal Chronic nonspecific musculoskeletal painpain

HypoCa and hypoPhosHypoCa and hypoPhos Osteomalasia –In AdultsOsteomalasia –In Adults

Defuse bone pain; pronounced in lower Defuse bone pain; pronounced in lower spine, lower extremities, and pelvisspine, lower extremities, and pelvis

Proximal Muscle weakness, muscle wastingProximal Muscle weakness, muscle wasting Rickets –In ChildrenRickets –In Children Secondary HyperparathyroidismSecondary Hyperparathyroidism

Risk of FracturesRisk of Fractures NEJM, 1992, Vol 327, No 23 1637-1642NEJM, 1992, Vol 327, No 23 1637-1642 France, Age 69-106 yoFrance, Age 69-106 yo 3270 ambulatory women3270 ambulatory women 1634 placebo, 1636 1.2g elemental Ca 1634 placebo, 1636 1.2g elemental Ca

+ 800 IU of vitamin D3 over 18 + 800 IU of vitamin D3 over 18 monthsmonths

Major outcome fractures:Major outcome fractures: Hip fx 43% lower in treatment groupHip fx 43% lower in treatment group Total non-vertebral fx 32% lowerTotal non-vertebral fx 32% lower

ObjectivesObjectives

Vitamin D MetabolismVitamin D Metabolism Actions of Vitamin DActions of Vitamin D Causes of Vitamin D deficiencyCauses of Vitamin D deficiency Prevalence of Vitamin D deficiencyPrevalence of Vitamin D deficiency Presentation of Vitamin D deficiencyPresentation of Vitamin D deficiency Diagnosis of Vitamin D deficiencyDiagnosis of Vitamin D deficiency Treatment of Vitamin D deficiencyTreatment of Vitamin D deficiency

Diagnosis of Vitamin D Diagnosis of Vitamin D DeficiencyDeficiency

Measure 25-hydroxyvitamin D levelsMeasure 25-hydroxyvitamin D levels <20 ng/ml is deficient, <10 ng/mL is <20 ng/ml is deficient, <10 ng/mL is

severesevere 30-50 ng/ml is optimal30-50 ng/ml is optimal

ObjectivesObjectives

Vitamin D MetabolismVitamin D Metabolism Actions of Vitamin DActions of Vitamin D Causes of Vitamin D deficiencyCauses of Vitamin D deficiency Prevalence of Vitamin D deficiencyPrevalence of Vitamin D deficiency Presentation of Vitamin D deficiencyPresentation of Vitamin D deficiency Diagnosis of Vitamin D deficiencyDiagnosis of Vitamin D deficiency Treatment of Vitamin D deficiencyTreatment of Vitamin D deficiency

Treatment of Vitamin D Treatment of Vitamin D DeficiencyDeficiency

Oral Vitamin D 50,000 IU once Oral Vitamin D 50,000 IU once weekly times 8 weeks, than 50,000 weekly times 8 weeks, than 50,000 IU once or twice monthly for IU once or twice monthly for prevention or 400 to 800 IU daliy prevention or 400 to 800 IU daliy

Sun exposure: Sun exposure: 1 minimal erythema dose (light pinkness 1 minimal erythema dose (light pinkness

of the skin) in a bathing suit = 20,000 IUof the skin) in a bathing suit = 20,000 IU Recommend 25% of the 1 minimal Recommend 25% of the 1 minimal

erythema dose (10-15 min midday sun 3 erythema dose (10-15 min midday sun 3 x a week on arms & legs or 1 hour/week x a week on arms & legs or 1 hour/week on arms & face)on arms & face)

Vitamin D deficiency linked to Vitamin D deficiency linked to other diseasesother diseases

MSMS Type I DMType I DM Cancers (Breast, prostate, and colon)Cancers (Breast, prostate, and colon)

Thought to regulate cell growth and differentiationThought to regulate cell growth and differentiation Degenerative Arthritis (Ann In Med 1996; 356-Degenerative Arthritis (Ann In Med 1996; 356-

9)9) Chronic fatigue/ DepressionChronic fatigue/ Depression Autoimmune (Sjogren’s, RA)Autoimmune (Sjogren’s, RA) IBD (Crohns)IBD (Crohns)

ConculsionsConculsions Vitamin D deficiency is prevalent at Vitamin D deficiency is prevalent at

all ages.all ages. The presentation of Vitamin D The presentation of Vitamin D

deficiency can be subtle.deficiency can be subtle. Sequla of Vitamin D deficiency are Sequla of Vitamin D deficiency are

many, with an end result of many, with an end result of increased fracture risk.increased fracture risk.

Treatment of Vitamin D deficiency is Treatment of Vitamin D deficiency is simple.simple.

ReferencesReferences Am. J. of Medicine; 02’, Vol 112, p659-662Am. J. of Medicine; 02’, Vol 112, p659-662 Annals of In. Med.; 96’, Vol 124, p400-406Annals of In. Med.; 96’, Vol 124, p400-406 JAMA; 1995, Vol 274, No 21, p1683-86JAMA; 1995, Vol 274, No 21, p1683-86 Mayo Clin. Proc., 2003, Vol. 78, p1463-70 Mayo Clin. Proc., 2003, Vol. 78, p1463-70 NEJM; 1992; Vol 327, No 23, p1637-1642NEJM; 1992; Vol 327, No 23, p1637-1642 NEJM; 1997; Vol 337, No 10, p671-676NEJM; 1997; Vol 337, No 10, p671-676 NEJM; 1998; Vol 338, No 12, p777-783NEJM; 1998; Vol 338, No 12, p777-783 NEJM; 2001; Vol 345, No 25, p1819-24NEJM; 2001; Vol 345, No 25, p1819-24 NEJM; 2003; Vol 348, No 15, p1503-04NEJM; 2003; Vol 348, No 15, p1503-04 Science; 2003; Vol 302, p1886-1888 Science; 2003; Vol 302, p1886-1888

References (cont)References (cont)

Harrison’s Principles of Internal Harrison’s Principles of Internal Medicine, 13Medicine, 13thth addition, p 2141-2145. addition, p 2141-2145.

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Any Questions?Any Questions?